Dental education at Dundee Dental Hospital and School - a notable past and inspiring future.

Dundee Dental Hospital and School has been present on Park Place, Dundee for over 100 years. During this time, it has been at the forefront of dental care and education, first as part of the University of St Andrews and subsequently the University of Dundee. This innovation continues with novel undergraduate curricula for dental and dental therapy students, providing early clinical experience and integrating clinical teaching with the appropriate sciences. We also offer several taught postgraduate programmes, popular particularly with international students. Dundee was at the forefront of the response to the COVID-19 pandemic, with the Scottish Dental Clinical Effectiveness Programme leading the world on guidance for safe clinical practice. Innovative solutions for the ongoing delivery of teaching and assessment also were developed. Research underpins teaching and the delivery of dental care and Dundee has an international reputation for its research portfolio. All of the above can only be achieved by close working relationships between the University and NHS, which will be strengthened further by the creation of the Dundee Dental Research Hospital and School. Our international reputation will continue to attract students and staff from across the world.

What lies behind the quality assurance of your materials?

In dentistry, all reputable manufacturers comply with international standards. This is important for quality assurance of dental materials. How such standards came into being and have evolved, however, is perhaps less well-known. This paper covers the necessity and formulation of standards and illustrates their application with reference to materials that may be considered as potential alternatives to dental amalgam. In addition, the uncertainties around such a framework following Brexit are summarised. Robust standards are essential for consumer protection and international trade.

Dental amalgam: the history and legacy you perhaps never knew?

Much has been written about dental amalgam. Over many years, it has served the profession well, yet on environmental grounds its use is being phased down. This article seeks to explore key milestones in the history and development of this versatile material, as well as highlighting how international standards have assisted in reducing environmental mercury contamination.

Amino acid-based H2S donors: N-thiocarboxyanhydrides that release H2S with innocuous byproducts.

A library of N-thiocarboxyanhydrides (NTAs) derived from natural amino acids with benign byproducts and controlled H2S-release kinetics is reported. Minimal acute in vitro toxicity was observed in multiple cell lines, while longer-term toxicity in cancer cells was observed, with slow-releasing donors exhibiting the greatest cytotoxic effects.

Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome.

Persulfides (R-SSH) have been hypothesized as potent redox modulators and signaling compounds. Reported herein is the synthesis, characterization, and in vivo evaluation of a persulfide donor that releases N-acetyl cysteine persulfide (NAC-SSH) in response to the prokaryote-specific enzyme nitroreductase. The donor, termed NDP-NAC, decomposed in response to E. coli nitroreductase, resulting in release of NAC-SSH. NDP-NAC elicited gastroprotective effects in mice that were not observed in animals treated with control compounds incapable of persulfide release or in animals treated with Na2 S. NDP-NAC induced these effects by the upregulation of beneficial small- and medium-chain fatty acids and through increasing growth of Turicibacter sanguinis, a beneficial gut bacterium. It also decreased the populations of Synergistales bacteria, opportunistic pathogens implicated in gastrointestinal infections. This study reveals the possibility of maintaining gut health or treating microbiome-related diseases by the targeted delivery of reactive sulfur species.

Targeted Program in an Academic Rheumatology Practice to Improve Compliance With Opioid Prescribing Guidelines for the Treatment of Chronic Pain.

OBJECTIVE: The Centers for Disease Control and Prevention (CDC) and many state governments have issued guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain. We sought to decrease practice variation and increase compliance with these guidelines in a tertiary academic rheumatology practice by developing an interdisciplinary opioid working group and using electronic health record (EHR)-integrated data feedback. METHODS: Division leadership and providers established shared goals at interdisciplinary meetings involving rheumatology, pain medicine, nursing, and pharmacy. Interventions included educational sessions on opioid prescribing guidelines and the sharing of individual de-identified prescribing patterns. An opioid dashboard page within the EHR allowed every provider to see individualized and division-wide data that tracked process measures based on CDC and state-specific guidelines. Baseline data from June to August 2017 were compared with monthly data through December 2018. RESULTS: At baseline, 40% of patients had an active opioid agreement (a Pennsylvania guideline and a New Jersey law), 25% had a urine drug screen result within 12 months of their most recent opioid prescription, and 24% had a concurrent benzodiazepine prescription. After 16 months, these percentages improved to 88%, 66%, and 16%, respectively. The average number of opioid tablets prescribed per month decreased from 59,733 to 48,966 (-18%; P = 0.02). CONCLUSION: Shared goals developed through interdisciplinary input and readily accessible data feedback can markedly increase provider compliance with national and state-specific guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain in rheumatology.

Fracture resistance of human roots filled with mineral trioxide aggregate mixed with phosphate-buffered saline, with and without calcium hydroxide pre-medication.

AIM: To compare the fracture strength of extracted human roots with apical plugs of mineral trioxide aggregate (MTA) mixed with either Ca- and Mg-free phosphate-buffered saline (PBS) or water, with and without calcium hydroxide (CH) canal pre-medication. METHODOLOGY: A total of 180 single-rooted human teeth were prepared to resemble immature roots and divided into groups (n = 20). The negative control received canal irrigation only, and the positive control received intracanal treatment with CH for either two or twelve weeks. MTA mixed with water was used in Group 1: (i) without CH pre-medication - MTA(W); (ii) after 2 weeks CH pre-medication - 2/52CH + MTA(W); and (iii) after 12-week CH pre-medication - 12/52 CH + MTA(W). MTA mixed with PBS was used in Group 2: (i) without CH pre-medication - MTA(PBS); (ii) after 2-week CH pre-medication - 2/52CH + MTA(PBS); and (iii) after 12-week CH pre-medication - 12/52 CH + MTA(PBS). A compressive force was applied to each root until the point of fracture. The results were analysed by the Kruskal-Wallis and Dunn's multiple comparisons tests (P < 0.05). RESULTS: There was no significant difference between groups MTA(W), MTA(PBS) and 2/52CH + MTA(PBS), and all three groups were significantly (P < 0.01, P < 0.05 and P < 0.05, respectively) more resistant to fracture than the negative control. Within Group 1, the samples that received two- (P < 0.01) and twelve-week (P < 0.001) CH pre-treatment were more prone to fracture than those which did not. No difference was found amongst the control groups. The roots of the MTA(PBS) group had a higher dependability (P < 0.05) than the MTA(W) group when compared by the Weibull modulus. The difference was also present when a 2-week CH pre-medication was used. CONCLUSIONS: Mineral trioxide aggregate mixed with Ca- and Mg-free phosphate-buffered saline had a significant strengthening effect on the fracture resistance of structurally weak roots, even when short-term calcium hydroxide pre-medication had been used. MTA mixed with water lost its strengthening effect on human roots when 2- or 12-week CH pre-treatment had been used. Use of CH dressing for up to 12 weeks had no negative effect on fracture resistance of human roots.

Polymeric persulfide prodrugs: Mitigating oxidative stress through controlled delivery of reactive sulfur species.

Related biologically to the known gasotransmitter hydrogen sulfide (H2S), persulfides (R-SSH) have recently been recognized as native signaling compounds and redox regulators in their own right. Reported here is the synthesis, characterization, and in vitro evaluation of a small molecule persulfide donor and its polymeric counterpart, both of which release N-acetyl cysteine persulfide (NAC-SSH) in response to esterases. The donors, termed EDP-NAC and poly(EDP-NAC), underwent controlled decomposition in response to porcine liver esterase, resulting in pseudo-first-order release half-lives of 1.6 h ± 0.3 h and 36.0 h ± 0.6 h, respectively. In cell experiments, slow-releasing poly(EDP-NAC) rescued H9C2 cardiomyocytes more effectively than EDP-NAC when cells were treated with 5-fluorouricil (5-FU), which induces sustained production of ROS. Neither EDP-NAC nor poly(EDP-NAC) rescued MCF-7 breast cancer cells from 5-FU-induced oxidative stress, suggesting that polymeric persulfide donors could be used as adjuvants to reduce the deleterious cardiotoxic effects of many chemotherapeutics.

Collection of extracted human teeth in decline: working knowledge and understanding of the Human Tissue Act by UK-registered dentists.

Introduction For many years, the dental profession has collected extracted human teeth for use in education and research. Since the enactment of the Human Tissue Act (HTA) in 2006, we have observed a fall in research outputs from the United Kingdom utilising extracted teeth for research.Aims To determine the working knowledge and understanding of the HTA of dentists in the UK who could potentially collect extracted teeth for use in teaching and research.Design A postal/online questionnaire.Materials and methods A printed questionnaire and pre-paid return envelope, which sought to assess both the knowledge and understanding of the participants concerning the HTA as it applied to the collection of extracted teeth, was mailed out to 500 UK-registered dentists. The potential participants were selected at random from the General Dental Council online registers.Results A total of 254 completed questionnaires were received (response rate = 50.8%). Prior to September 2006, 65.6% of respondents had collected teeth. After this, only 37.8% did so. This was statistically significant (P <0.001).Conclusions Confusion surrounded the collection and use of extracted teeth, which hampered dental education and research. To address this, there is a need for clarity on the legal issues.

Novel Confocal-Laser-Scanning-Microscopy and conventional measures investigating eroded dentine following dentifrice dab-on and brushing abrasion.

OBJECTIVES: To validate novel non-contacting Confocal-Laser-Scanning-Microscopy (CLSM) methodology with conventional Contacting Profilometry (CP) measures investigating brushing or dab-on of stannous-fluoride dentifrice on early aggressive dentine erosion. METHODS: 75 polished human dentine samples were prepared and eroded in agitated 6% citric acid then randomly allocated into 5 intervention groups; artificial saliva control (1); controlled use of a pressure sensitive counter-rotating oscillatory powered toothbrush with sodium-fluoride NaF (2) or stannous-fluoride SnF2 (3), and dab-on application of NaF (4) or SnF2 (5). Samples underwent three cycles of intervention and 2-min agitated 6 % citric acid challenges. CLSM images were taken and 3D reconstructions produced of step height using a developed software algorithm. In addition, 20 % samples were randomised and profiled using CP to measure step height and surface roughness. Vickers's diamond micro-hardness testing was carried out on all samples. RESULTS: Comparing CLSM and CP; Pearson correlation was 0.77 and Intra-class correlation 0.81 (p = 0.01). There were no significant statistical differences in step height between groups using both CLSM and CP. From baseline, SnF2 brushing (3) increased micro-hardness more than control (1) (p = 0.03), NaF (4) and SnF2 dab-on (5) (p ≤ 0.001), and increased surface roughness more than control (p = 0.02), NaF brushing (2) and NaF dab-on (4) (p ≤ 0.017). Dab-on of SnF2 (5) produced rougher surfaces than control (1) (p = 0.014) and reduced hardness compared with NaF brushing (p = 0.04). CONCLUSIONS: Good agreement and correlation exists between CLSM and CP measures in dentine. There were no significant differences in surface loss after interventions between groups. Compared with control, SnF2 application increased dentine surface roughness and SnF2 controlled powered brushing application increased dentine hardness, likely caused by exposure of uneroded dentine. CLINICAL SIGNIFICANCE: Isosurfaces produced using CLSM can be used to represent dentine step height loss. They show good correlation and agreement with conventional CP measures, following early aggressive erosion-abrasion cycles of dentine. The CLSM and computer algorithm therefore provides an accurate, standalone and non-contacting three-dimensional measurement of early dentine wear. Stannous-fluoride brushing, and dab-on application offer no benefits following early aggressive erosion in dentine. To reduce dentine wear, limiting erosive challenges and avoiding brushing post-erosion is advised.

Self-Amplified Depolymerization of Oligo(thiourethanes) for the Release of COS/H2S.

Herein we report the self-amplified depolymerization of an aryl oligo(thiourethane) (OTU) for the release of COS/H2S. The OTU was synthesized via polyaddition of 4-isothiocyanatobenzyl alcohol and end-capped with an aryl azide. The aryl azide chain-end was reduced by tris(2-carboxyethyl)phosphine or H2S to the corresponding aniline, resulting in depolymerization (i.e., self-immolation) and the release of COS/H2S. Depolymerization was monitored by 1H NMR and UV-Vis spectroscopy, and the released COS was converted into H2S by the ubiquitous enzyme carbonic anhydrase in aqueous media.

Self-Immolative Prodrugs: Effective Tools for the Controlled Release of Sulfur Signaling Species.

H2S, persulfides (R-SSH), and related sulfur species have recently received attention due to the pronounced physiological effects they elicit. Delivering sulfur signaling molecules in a controlled manner presents many challenges, as many available donors have short half-lives, lack water solubility, and exhibit poor trigger specificity. Self-immolative prodrugs provide a unique ability to impart stability to H2S precursors and persulfides while allowing for trigger specificity by tuning the functional group installed on the self-immolative linker. This strategy has proven successful in delivering sulfur signaling species under specific conditions and may lead to the further elucidation of persulfide interactions within biological systems, affording effective therapeutics.

Functional N-Substituted N-Thiocarboxyanhydrides as Modular Tools for Constructing H2S Donor Conjugates.

We report a synthetic route toward a family of functional COS/H2S-releasing N-substituted N-thiocarboxyanhydrides (NTAs) with functionalities to accommodate popular conjugation reactions, including olefin cross metathesis, thiol-ene, and copper-catalyzed azide-alkyne cycloaddition. The N-substituted NTAs were attached to small molecules, polymers, and a protein to synthesize novel H2S donors convergently. All conjugates showed sustained H2S release kinetics.

A Persulfide Donor Responsive to Reactive Oxygen Species: Insights into Reactivity and Therapeutic Potential.

Persulfides (RSSH) have been hypothesized as critical components in sulfur-mediated redox cycles and as potential signaling compounds, similar to hydrogen sulfide (H2 S). Hindering the study of persulfides is a lack of persulfide-donor compounds with selective triggers that release discrete persulfide species. Reported here is the synthesis and characterization of a ROS-responsive (ROS=reactive oxygen species), self-immolative persulfide donor. The donor, termed BDP-NAC, showed selectivity towards H2 O2 over other potential oxidative or nucleophilic triggers, resulting in the sustained release of the persulfide of N-acetyl cysteine (NAC) over the course of 2 h, as measured by LCMS. Exposure of H9C2 cardiomyocytes to H2 O2 revealed that BDP-NAC mitigated the effects of a highly oxidative environment in a dose-dependent manner over relevant controls and to a greater degree than common H2 S donors sodium sulfide (Na2 S) and GYY4137. BDP-NAC also rescued cells more effectively than a non-persulfide-releasing control compound in concert with common H2 S donors and thiols.

A review of hydrogen sulfide (H2S) donors: Chemistry and potential therapeutic applications.

Hydrogen sulfide (H2S) is a ubiquitous small gaseous signaling molecule, playing an important role in many physiological processes and joining nitric oxide and carbon monoxide in the group of signaling agents termed gasotransmitters. Endogenous concentrations of H2S are generally low, making it difficult to discern precise biological functions. As such, probing the physiological roles of H2S is aided by exogenous delivery of the gas in cell and animal studies. This need for an exogenous source of H2S provides a unique challenge for chemists to develop chemical tools that facilitate the study of H2S under biological conditions. Compounds that degrade in response to a specific trigger to release H2S, termed H2S donors, include a wide variety of functional groups and delivery systems, some of which mimic the tightly controlled endogenous production in response to specific, biologically relevant conditions. This review examines a variety of H2S donor systems classified by their H2S-releasing trigger as well as their H2S release profiles, byproducts, and potential therapeutic applications.

Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with Benign Byproducts.

Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.

Investigating the addition of collagen and its integrin binding sequence (RGD) to glass polyalkenoate: In terms of material and cellular properties to explore a more biocompatible method of root caries restoration.

AIMS: Placement of a restoration to treat root caries disrupts many tissues. There is scope for the restorative material to interact with these to augment reductions in micro leakage afforded by an adhesive restorative material. OBJECTIVES: 1) To investigate the effects of incorporating bioactive molecules into a glass polyalkenoate (GPA) 2) To quantify the changes in physical properties of the material. METHODS: Biocompatibility of the GPA cement (Chemfil Superior, Dentsply De Trey, Konstanz, Germany) in unmodified and modified forms was ascertained using cell culture techniques. The optimum concentration of bioactive components required to promote cell attachment was determined indirectly by quantification and localisation of the fibroblast marker vimentin. The properties of surface hardness, compressive strength and adhesive bond strength were also determined prior to and following addition of the bio-additives: collagen type I and a pentapeptide containing Arg-Gly-Asp (RGD). RESULTS: Addition of Type I Collagen (100µg/ml) and RGD (5mg/ml) to ChemFil Superior had no statistically significant effect upon the compressive strength and bond strength to bovine enamel but significantly (P<0.05) increased the materials shore hardness. The addition of RGD to ChemFil Superior increased most the expression of vimentin, indicating that the cells had become more fibroblastic. This may be indicative of increased synthesis of extracellular matrix macromolecules with the potential to foster adhesion of the modified glass polyalkenoate to distracted gingival tissues. CONCLUSIONS: The results suggest that addition of bioactive molecules to GPA cement for subgingival restorations has potential clinical applications. CLINICAL SIGNIFICANCE: It is possible to envisage that the additions, as described in this paper, could foster the attachment of displaced gingival tissues to GPA restorative materials placed subgingivally where root caries has been treated. This would offer potential to form a seal around the restoration by the attached gingival tissues avoiding a periodontal pocket and depriving residual cariogenic bacteria of a nutrient supply. Further investigation of the effects upon other similar materials of such additions is warranted.