SARS-CoV-2 infection causes periodontal fibrotic pathogenesis through deregulating mitochondrial beta-oxidation.

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The SARS-CoV-2 virus mutates predominantly in the spike proteins, whilst the other key viral components usually remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. Fibroblasts are the major cell type inside periodontal ligament (PDL) and express the SARS-CoV-2 receptor: Angiotensin-converting enzyme 2 (ACE2), whose expression level can increase upon bacterial infection hence potentially provide a direct route of SARS-CoV-2 infection to PDL fibroblasts. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human fibroblasts. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was simultaneously induced with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial ß-oxidation in the fibroblasts. Fatty acid ß-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.

Dental education in primary care: 14 years of Peninsula Dental School.

Peninsula Dental School, established in 2006, was the UK's first new dental school in 40 years. It had the freedom to develop a completely new dental education curriculum planned on pedagogic thinking, designed to equip the dental care professionals of the twenty-first century. This was based on three distinct pillars: professionalism (developing a student's trust in their own autonomy); dental skills of the highest order (not just technical skills but also communication skills); and social engagement. As such, a truly innovative approach to dental education was created that has strong roots in evidence.This paper describes the University of Plymouth Peninsula Dental School's achievements against these initial objectives under the following areas: training in primary care; a novel spiralling integrated curriculum and assessments; facilities reaching out to deliver patient care; bringing meaningful patient contact to students from the earliest months of their course; embedding community engagement within the curriculum; development of Peninsula Dental Social Enterprise; and team working, training a variety of dental care profession students side by side.The University of Plymouth Peninsula Dental School, working with all its partners, has successfully pioneered and delivered significant changes in the field of education and continues to strive to further develop these and more for the future.

Deletion of RBP-Jkappa gene in mesenchymal cells causes rickets like symptoms in the mouse.

Crosstalk between different signalling pathways provide deep insights for how molecules play synergistic roles in developmental and pathological conditions. RBP-Jkappa is the key effector of the canonical Notch pathway. Previously we have identified that Wnt5a, a conventional non-canonical Wnt pathway member, was under the direct transcriptional control of RBP-Jkappa in dermal papilla cells. In this study we further extended this regulation axis to the other two kind of skeletal cells: chondrocytes and osteoblasts. Mice with conditional mesenchymal deletion of RBP-Jkappa developed Rickets like symptoms. Molecular analysis suggested local defects of Wnt5a expression in chondrocytes and osteoblasts at both mRNA and protein levels, which impeded chondrocyte and osteoblast differentiation. The defects existing in the RBP-Jkappa deficient mutants could be rescued by recombinant Wnt5a treatment at both cellular level and tissue/organ level. Our results therefore provide a model of studying the connection of Notch and Wnt5a pathways with Rickets. Supplementary Information: The online version contains supplementary material available at 10.1007/s44194-022-00007-w.

'It is difficult to think about becoming what you have never seen': Black students' reflections around a career in academic dentistry.

This opinion piece considers the national representation of the Black population in the United Kingdom in an academic career in dentistry and draws on engagement with Black dental students to see what their perceptions of this are. Black people are under-represented in dentistry as a whole and the number of Black academics who teach dentistry to an increasing number of aspiring young Black dental students is exceedingly low. Black dental students do not see themselves represented by their teachers and therefore 'it is difficult to think about [them] becoming what [they] have never seen'. Black dental students themselves have started initiatives to establish a strong support network of aspiring and qualified Black dentists. Dialogue with them showcases that while there are pathways into an academic career in dentistry, these appear unclear to them. This piece is intended to raise awareness of these issues, in the knowledge that with mentoring, role modelling and dialogue, pathways may become clearer, opportunities may arise that were previously not considered and the national picture may one day change.

The dental therapist's role in a 'shared care' approach to optimise clinical outcomes.

Introduction Dental therapists have a key role to play in the provision of dentistry in the UK. The Dental Workforce Advisory Group has reported this is relevant in multiple areas, including prevention and care in young children, and to support dentists in providing advanced and routine treatment for complex adult patients within the wider collaborative dental team. There remain diverse and multiple barriers and challenges to utilising the optimal scope of the dental therapist in general practice. In 2013, the General Dental Council introduced direct access (DA) legislation in the UK. By utilising the potential of dental therapists, some of the above challenges could be overcome and the DA approach optimised.Aims The purpose of this article through presenting clinical cases is to demonstrate the full scope of practice of the dental therapist and highlight how clinical outcomes can be optimised for patients when a 'shared care' approach is followed.Conclusions Notwithstanding the complexities of the financial implications practice owners face, through knowledge and understanding of the role and scope of the dental therapist within the wider dental team, optimal treatment of dental patients in the UK can be encouraged.

Addressing racial inequalities in dental education: decolonising the dental curricula.

The aim of this paper is to highlight the impact of racial disparities on the educational experiences of Black and minority ethnic students in healthcare education. Attainment gaps and barriers to career progression for minority ethnic home students in the United Kingdom have been recognised for decades, but little progress has been made to address these issues. Students and staff in higher education have been campaigning for 'decolonisation of the curriculum' to improve inclusivity and representation. These trends are being mirrored in medical education and there is growing recognition to decolonise the medical curricula. This would improve the educational experience and attainment of minority ethnic students and doctors, and would also help to address disparities in healthcare provision for minority ethnic patients. The context for decolonisation of the dental curricula is provided, followed by a discussion on the benefits, challenges and strategies for such decolonisation.

Multimorbidity and oral health: need for new models of care.

Multimorbidity is defined as patients living with two or more chronic health conditions. The prevalence of multimorbidity is increasing, driven by the ageing population, and represents a major challenge to all healthcare systems because these patients are heavy users of services. The link with oral health is growing although there is need for further robust evidence. There is also need for new models of care to address oral health in patients with multimorbidity.

Transfer of basic science knowledge in a problem-based learning curriculum.

AIM: The aim of this study was to evaluate transfer of basic science knowledge for clinical application in our BDS programme by exploring the correlations between student performance in integrated dental science (IDS) examinations and applied dental knowledge (ADK) tests. METHODS: Numeric test scores were drawn from summative IDS and ADK assessments undertaken by BDS students spanning six academic years (2013-14 to 2018-19) for two cohorts (2013 and 2014). The data included a total of 13 test scores for each cohort with four IDS tests, taken in Years 1 and 2, and nine ADK tests taken in Years 3, 4 and 5. RESULTS: The sample included 120 students across both cohorts with 65 females (54%) and 55 males (46%). The correlation coefficients between the successive tests and the combinations of IDS and ADK scores were positive, all being greater than 0.48, and all being significantly correlated (P < .001). Regarding correlation between standardised averages across all IDS tests and all ADK tests, performance remained significantly correlated: (2013 cohort: r (53) = .667, P < .001; 2014 cohort: r (50) = .700, P < .001). CONCLUSIONS: The results of this study show that the students' knowledge of basic sciences correlates with their applied dental knowledge and may offer a predictive value. These findings may be attributed to a PBL curriculum and student-led learning at our school.

Antibacterial properties of silver nanoparticles grown in situ and anchored to titanium dioxide nanotubes on titanium implant against Staphylococcus aureus.

Medical grade titanium alloy, Ti-6Al-4V, with TiO2 nanotubes (TiO2-NTs) grown on the surface and then decorated with silver nanoparticles (Ag NPs) is proposed to enhance the antimicrobial properties of the bone/dental implants. However, the decoration with Ag NPs is not consistent and there are concerns about the direct contact of Ag NPs with human tissue. The aim of this study was to achieve a more even coverage of Ag NPs on TiO2-NTs and determine their biocidal properties against Staphylococcus aureus, with and without a top coat of nano hydroxyapatite (nHA). The decoration with Ag NPs was optimised by adjusting the incubation time of the TiO2-NTs in a silver ammonia solution, and using biocompatible δ-gluconolactone as a reducing agent. The optimum incubation in silver ammonia was 7 min, and resulted in evenly distributed Ag NPs with an average diameter of 47.5 ± 1.7 nm attached to the surface of the nanotubes. The addition of nHA did not compromise the antimicrobial properties of the materials; high-resolution electron microscopy showed S. aureus did not grow on the composite with nHA and with >80% biocidal activity measured by the LIVE/DEAD assay, also limited lactate production. Dialysis experiment confirmed the stability of the coatings, and showed a slow release of dissolved silver (3.27 ± 0.15 µg/L over 24 h) through the top coat of nHA.

How does dyslexia impact on the educational experiences of healthcare students? A qualitative study.

AIMS: To explore the impact of dyslexia on the educational experiences of undergraduate students in medicine, dentistry, dental therapy and biomedical sciences. METHODS: It was a qualitative study based on semi-structured interviews. The study was conducted at the Faculty of Medicine and Dentistry at a University in the South West region of the United Kingdom. Purposive sampling was used, and the participants included undergraduate students from the schools of medicine, dentistry and biomedical sciences. RESULTS: The sample consisted of fifteen undergraduate students including five from medicine; four from dentistry; three from dental therapy; and three from biomedical sciences. All students had a formal diagnosis of Dyslexia. The students shared their views and experiences regarding disclosure, transition into the university, learning environments, assessments and challenges after graduation. CONCLUSIONS: This is the first study to explore the impact of dyslexia on the educational experiences of healthcare students from multiple programmes in a variety of educational settings. The findings show that the students were confident regarding disclosure of their dyslexia and had a formal diagnosis of dyslexia established during their school years. Although the participants experienced typical academic difficulties associated with dyslexia, problem-based learning (PBL) was perceived to be enjoyable and less stressful than traditional lectures and no specific challenges were reported in acquisition of clinical, communication and team-working skills.

The biocompatibility of silver and nanohydroxyapatite coatings on titanium dental implants with human primary osteoblast cells.

Silver nanoparticles (Ag NPs) are antimicrobial, with potential uses in medical implants, but Ag NPs alone can also be toxic to mammalian cells. This study aimed to enhance the biocompatibility of Ag NP-coated titanium dental implants with hydroxyapatite (HA) applied to the surface. Ti6Al4V discs were coated with Ag NPs, Ag NPs plus HA nanoparticles (Ag + nHA), or Ag NPs plus HA microparticles (Ag + mHA). The stability of coatings was explored and the biocompatibility with primary human osteoblasts over 7 days. Results showed that Ti6Al4V discs were successfully coated with silver and HA. The primary particle size of nHA and mHA were 23.90 ±â€¯1.49 nm and 4.72 ±â€¯0.38 µm respectively. Metal analysis showed that underlying silver coatings remain stable in DMEM culture media, but the presence of FBS in the media caused some initial (clinically beneficial) release of dissolved silver. With additions of HA, osteoblasts were adherent, had normal morphology, negligible lactate dehydrogenase (LDH) leak, and showed alkaline phosphatase (ALP) activity. Cell viability was around 70% throughout the Ag + nHA treatment. Overall, the implants coated with Ag + nHA maintained a higher degree of biocompatibility compared to those coated with Ag + mHA, or Ag NPs alone, suggesting the former has a benefit for clinical use.

Carbon Nanotube Reinforced Hydroxyapatite Nanocomposites As Bone Implants: Nanostructure, Mechanical Strength And Biocompatibility.

PURPOSE: Hydroxyapatite (HA) is a biologically active ceramic which promotes bone growth, but it suffers from relatively weak mechanical properties. Multi-walled carbon nanotubes (MWCNTs) have high tensile strength and a degree of stiffness that can be used to strengthen HA; potentially improving the clinical utility of the bone implant. METHODS: HA was precipitated by the wet precipitation method in the presence of pristine (p) or functionalised (f) MWCNTs, and polyvinyl alcohol (PVA) or hexadecyl trimethyl ammonium bromide (HTAB) as the surfactant. The resulting composites were characterised and the diametral tensile strength and compressive strength of the composites were measured. To determine the biocompatibility of the composites, human osteoblast cells (HOB) were proliferated in the presence of the composites for 7 days. RESULTS: The study revealed that both the MWCNTs and surfactants play a crucial role in the nucleation and growth of the HA. Composites made with f-MWCNTs were found to have better dispersion and better interaction with the HA particles compared to composites with p-MWCNTs. The mechanical strength was improved in all the composites compared to pure HA composites. The biocompatibility study showed minimal LDH activity in the media confirming that the composites were biocompatible. Similarly, the ALP activity confirmed that the cells grown on the composites containing HTAB were comparable to the control whereas the composites containing PVA surfactant showed significantly reduced ALP activity. CONCLUSIONS: The study shows that the composites made of f-MWCNTs HTAB are stronger than pure HA composites and biocompatible making it a suitable material to study further.

Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.

Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1's function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.

Multilayered composite coatings of titanium dioxide nanotubes decorated with zinc oxide and hydroxyapatite nanoparticles: controlled release of Zn and antimicrobial properties against Staphylococcus aureus.

Purpose: This study aimed to decorate the surface of TiO2 nanotubes (TiO2 NTs) grown on medical grade Ti-6Al-4V alloy with an antimicrobial layer of nano zinc oxide particles (nZnO) and then determine if the antimicrobial properties were maintained with a final layer of nano-hydroxyapatite (HA) on the composite. Methods: The additions of nZnO were attempted at three different annealing temperatures: 350, 450 and 550 °C. Of these temperatures, 350°C provided the most uniform and nanoporous coating and was selected for antimicrobial testing. Results: The LIVE/DEAD assay showed that ZnCl2 and nZnO alone were >90% biocidal to the attached bacteria, and nZnO as a coating on the nanotubes resulted in around 70% biocidal activity. The lactate production assay agreed with the LIVE/DEAD assay. The concentrations of lactate produced by the attached bacteria on the surface of nZnO-coated TiO2 NTs and ZnO/HA-coated TiO2 NTs were 0.13±0.03 mM and 0.37±0.1 mM, respectively, which was significantly lower than that produced by the bacteria on TiO2 NTs alone, 1.09±0.30 mM (Kruskal-Wallis, P<0.05, n=6). These biochemical measurements were correlated with electron micrographs of cell morphology and cell coverage on the coatings. Conclusion: nZnO on TiO2 NTs was a stable and antimicrobial coating, and most of the biocidal properties remained in the presence of nano-HA on the coating.

To accept or decline academic remediation: What difference does it make?

Introduction: Academic remediation offered after failure in a knowledge-based progress-test assessment is voluntary and involves student-centered individualized support that helps students to learn most effectively for themselves. This paper explores whether accepting or declining the offer of academic remediation given to struggling students impacts their outcomes both short-term and longitudinally. Method: Data was collated from 2015-16, 2016-17, and 2017-18 and included all students offered academic remediation in the third, fourth, and fifth years of a five-year Dentistry program. Z-scores for each stage and test were calculated and centered on a triggering point; the point at which the offer of remediation was made. These students' average performance post-trigger test and longitudinal performance were analyzed. Results: While performance for both groups significantly improved for the immediate post-trigger test after academic remediation, those that accepted remediation sustained longitudinal improvements across subsequent tests compared to those that declined remediation. Discussion: Through the academic remediation support process students appear to increase their mastery of "learning to learn" and are able to implement sustainable effective learning strategies to carry with them throughout their program. Conclusion: Students who accept academic remediation maintain a more successful academic profile compared to those that do not take advantage of this.

Prominin-1 controls stem cell activation by orchestrating ciliary dynamics.

Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol-binding membrane glycoprotein, Prominin-1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.

Impact of Progress testing on the learning experiences of students in medicine, dentistry and dental therapy.

AIMS: To investigate the impact of progress testing on the learning experiences of undergraduate students in three programs namely, medicine, dentistry and dental therapy. METHODS: Participants were invited to respond to an online questionnaire to share their perceptions and experiences of progress testing. Responses were recorded anonymously, but data on their program, year of study, age, gender, and ethnicity were also captured on a voluntary basis. RESULTS: A total of 167 participants completed the questionnaire yielding a response rate of 27.2% (n = 167). These included 96 BMBS students (27.4%), 56 BDS students (24.7%), and 15 BScDTH students (39.5%). A 3 -Program (BMBS, BDS, BScDTH) by 8-Topic (A-H) mixed analysis of variance (ANOVA) was conducted on the questionnaire responses. This revealed statistically significant main effects of Program and Topic, as well as a statistically significant interaction between the two (i.e. the pattern of topic differences was different across programs). CONCLUSIONS: Undergraduate students in medicine, dentistry, and dental therapy and hygiene regarded PT as a useful assessment to support their learning needs. However, in comparison to students in dentistry and dental therapy and hygiene, the perceptions of medical students were less positive in several aspects of PT.

Anodised TiO2 nanotubes as a scaffold for antibacterial silver nanoparticles on titanium implants.

Medical grade titanium alloy is widely used for bone/dental implants, but the material alone has no innate antimicrobial properties that would reduce infection risk following surgery. However, silver nanoparticles (Ag NPs) are known to be antibacterial. This study investigated the growth of Ag NPs on titanium dioxide nanotubes (TiO2 NTs) on Ti-6Al-4V discs. The TiO2 NTs were grown on the Ti alloy using an electrochemical method, and then decorated with Ag NPs. The Ag NPs were synthesised by chemical reduction using δ-gluconolactone. A silver ammonia solution (silver nitrate + liquid ammonia) was used as the source of silver. Two separate approaches were used: (1) The δ-gluconolactone was mixed with the silver ammonia and then exposed to the TiO2 NTs (the 'mixing method'), which produced micron-sized clusters of the Ag NPs. (2) The TiO2 NTs were exposed to the silver ammonia first and then to δ-gluconolactone (the 'sequential addition method'), which resulted in the formation of nano-sized clusters of the nanoparticles. The Ag-TiO2 composites were confirmed by scanning electron microscopy and the elements analysed using energy dispersive X-ray spectroscopy (EDS). The composite coatings were exposed to a simulated body fluid for 24 h in order to determine the total Ag released. The release from the micron-sized clusters from the mixing method (14.6 ±â€¯0.67 ppm) was higher than that from the nano-sized clusters (4.05 ±â€¯0.36 ppm) when 0.015 M of silver ammonia was used. Additionally, Staphylococcus aureus, was cultured on the composite coatings for 24 h. Both the micron- and nano-sized clusters of the Ag NPs were found to be antibacterial using the Live/Dead assay. Overall, δ-gluconolactone was successfully used to reduce silver to Ag NPs on the surface of TiO2 NTs. The sequential addition method was the preferred method of synthesis because of its slower silver release, better coverage of the Ag-NPs on the TiO2 NTs and strong antibacterial properties.

Use of Progress Testing in a UK Dental Therapy and Hygiene Educational Program.

Progress testing provides a longitudinal assessment of the development and sustainability of students' knowledge at regular intervals over the duration of an educational program. Comparisons of performance on successive tests are used to monitor growth in knowledge. The aim of this study was to evaluate the effects of progress testing in an undergraduate program for dental therapy and hygiene (DTH) students in the United Kingdom as the main tool for academic assessment. Data were collected for progress tests of all 38 DTH students from 2015 to 2017. Each test consisted of 100 single best answer multiple-choice items with accompanying vignette. The students chose their answer from five options. A score of 1 was awarded for a correct answer, -0.25 for an incorrect answer, and 0 for don't know (DK). Three cohorts of DTH students were included in the study, and seven progress tests were conducted over a period of three years. Analysis of performance showed growth in knowledge across successive years, with the largest increase in knowledge in the transition from Year 1 to Year 2 and concomitant reduction in incorrect and DK responses. This was a pioneering study to report the establishment and use of progress testing among undergraduate DTH students. Notwithstanding the challenges involved, the study found merit in further exploring the use of progress testing for students in the DTH program.

Correlations Between Final-Year Dental Students' Performance on Knowledge-Based and Clinical Examinations.

Dental students are assessed using a range of methods in their final-year examinations. The aim of this study was to explore the correlations and predictive value of final-year dental students' performance on knowledge-based and clinical assessments. Examination data related to applied dental knowledge (ADK), exit case presentation (CP), and integrated structured clinical examination (ISCE) assessments for five consecutive cohorts of final-year students at one U.K. dental school from 2011-12 to 2015-16 were collated. The relationships between the scores produced by each assessment were investigated to explore the relative contributions of each to the understanding of students' abilities across the domains. The study utilized data from all 304 students: 147 (48.4%) females and 157 (51.6%) males. Significant positive correlations were found between ISCE and ADK performance (r(391)=0.42, p<0.001) as well as between ISCE and CP (r(391)=0.44, p<0.001). In addition, both ADK performance and CP performance were significant predictors (at p<0.001) of ISCE performance. This study provides important information about the relationship between these students' performance across knowledge (ADK) and clinical (ISCE and CP) domains and highlights their predictive value. Further research is required to establish if these findings can be generalized and to explore the correlations between performance of dental students before and after graduation.