Antimicrobial Efficacy of Different Irrigant Solutions Using a Novel Biofilm Model: An In Vitro Confocal Laser Scanning Microscopy Experiment.

AIM: To determine the ability of different irrigation solutions to biomechanically remove Enterococcus faecalis biofilm from a novel artificial root canal model during chemomechanical preparation. METHODS: High resolution micro-computer-tomography scans of a mandibular molar's mesial root were used to produce 50 identical 3D-printed resin root canal models. These were cultured with E.faecalis over seven days to generate biofilm and subjected to chemomechanical preparation using: saline; 17% ethylenediaminetetraacetic acid (EDTA) or 2% sodium hypochlorite (NaOCl) alongside positive/negative controls (n = 10). Canals were prepared to 40/.06 taper, with 1 mL irrigation between instruments, followed by 5 mL penultimate rinse, 30 s ultrasonic activation and 5 mL final rinse. Residual biofilm volume (pixels) was determined following immunofluorescent staining and confocal-laser-scanning-microscopy imaging. Statistical comparisons were made using Kruskal-Wallis with post-hoc Dunn's tests (α ⟨0.05). RESULTS: In all canal thirds, the greatest biofilm removal was observed with NaOCl, followed by EDTA and saline. The latter had significantly higher E.faecalis counts than NaOCl and EDTA (P ⟨0.01). However, no statistical differences were found between EDTA and NaOCl or saline and positive controls (P ⟩0.05). CONCLUSIONS: Within limitations of this model, 17% EDTA was found to be as effective as 2% NaOCl at eradicating E.faecalis biofilm following chemomechanical preparation. Further investigations with multi-species biofilms are encouraged.

Curriculum content and assessment of pre-clinical dental skills: A survey of undergraduate dental education in Europe.

INTRODUCTION: Since 1981, the qualifications for various healthcare professionals across the European Union have enjoyed mutual recognition in accordance with the EU Directive 81/1057/EEC. Whilst the directive includes dental practitioners, it is recognised that significant variation exists in curriculum structure, content and scope of practice across institutions. This article aimed to explore pan-European practice in relation to curriculum content, teaching and learning strategies and assessment of pre-clinical dental skills. METHOD: A request to complete an online questionnaire, in English, was sent electronically to skills leads at all Association of Dental Education in Europe member schools. The questionnaire collected information in relation to institution and country, regulatory requirements to demonstrate safety, details of specific pre-clinical skills courses, learning materials and teaching staff. RESULTS: Forty-eight institutions, from 25 European countries responded. Seven countries (n=7, 28%) reported no requirement to demonstrate student operative safety prior to patient treatment. Several core and operative clinical skills are common to the majority of institutions. The most commonly taught core skills related directly to the clinical environment such as cross-infection control and hand washing. The least common were skills that indirectly related to patient care, such as communication skills and working as a team. CONCLUSION: There are clear differences within European pre-clinical dental education, and greater efforts are needed to demonstrate that all European students are fit to practice before they start treating patients. Learning outcomes, teaching activities and assessment activities of pre-clinical skills should be shared collaboratively to further standardise curricula.

Guidelines for the organisation of continuing professional development activities for the European dentist.

AIM: Free movement of dental professionals across the European Union calls for more uniform continuing education in dentistry to ensure up-to-date, high-quality patient care and patient safety. This article provides guidelines for the management and delivery of high-quality continuing professional development (CPD) by European dental schools and other CPD providers. METHOD: The guidelines are based on an extensive literature inventory, a survey of existing practices (both available as separate publications), discussions during meetings of the Association for Dental Education in Europe in 2011 and 2012 and debate amongst the members of the DentCPD project team representing six dental schools. RESULTS: On the basis of the literature review, survey and discussions, we recommend that (i) every dentist should be given the opportunity for CPD, (ii) providers should be quality-approved and impartial, (iii) educators should be approved, impartial, suitably trained, and with educational expertise, (iv) the mode of CPD delivery should suit the educational activity, with clear learning objectives or outcomes, (v) effort should be made to assess the learning, (vi) participant feedback should be collected and analysed to inform future developments and (vii) uniform use of the pan-European system of learning credit points (ECTS) should be implemented. CONCLUSION: Implementation of these guidelines should make dental CPD more transparent to all relevant parties and facilitate the transferability of earned credits across the European Union. It will also enable better quality control within dentistry, resulting in enhanced dental care and ultimately the improvement in patient safety.

The development of an exemplar e-module for the continuing professional development of European dentists.

AIM: To present the development of an exemplar e-module for dental continuing professional development (CPD) provided by dental schools and other dental educational providers. MATERIALS AND METHODS: The exemplar e-module covered the topic of 'Sterilisation and cross-infection control in the dental practice' as this is one of the most recommended topics for dental CPD in Europe. It was developed by a group of topic experts, adult learning and distance learning experts and a technical developer. Major concerns were pedagogy, interoperability, usability and cost reduction. Open-source material was used to reduce the cost of development. RESULTS: The e-module was pre-piloted in dental practitioners for usability and then evaluated by experts in the field and dental academics through an electronic questionnaire and an online presentation and discussion at the ADEE 2012 Special Interest Group on DentCPD-Lifelong learning. This facilitated refinement before final production. A Creative Commons License was implemented to ensure the developers' rights and facilitate wider distribution and access to CPD providers. DISCUSSION AND CONCLUSIONS: The e-module was developed according to well-defined pedagogical and technical guidelines for developing e-learning material for adult learners. It was structured to promote self-study by directing learners through their study, promoting interaction with the material, offering explanation and providing feedback. Content validity was ensured by extensive review by experts. The next step would be to expand the evaluation to practising dentists in various countries after relevant translations, and adaptations to local policies have been made.

Recommendations for the development of e-modules for the continuing professional development of European dentists.

AIMS: To provide evidence-based and peer-reviewed recommendations for the development of dental continuing professional development (CPD) learning e-modules. METHODS: The present recommendations are consensus recommendations of the DentCPD project team and were informed by a literature research, consultations from e-learning and IT expert, discussions amongst the participants attending a special interest group during the 2012 ADEE meeting, and feedback from the evaluation procedures of the exemplar e-module (as described in a companion paper within this Supplement). The main focus of these recommendations is on the courses and modules organised and offered by dental schools. RESULTS AND DISCUSSION: E-modules for dental CPD, as well as for other health professionals' continuing education, have been implemented and evaluated for a number of years. Research shows that the development of e-modules is a team process, undertaken by academics, subject experts, pedagogists, IT and web designers, learning technologists and librarians. The e-module must have clear learning objectives (outcomes), addressing the learners' individual needs, and must be visually attractive, relevant, interactive, promoting critical thinking and providing feedback. The text, graphics and animations must support the objectives and enable the learning process by creating an attractive, easy to navigate and interactive electronic environment. Technology is usually a concern for learners and tutors; therefore, it must be kept simple and interoperable within different systems and software. The pedagogical and technological proficiency of educators is of paramount importance, yet remains a challenge in many instances. CONCLUSIONS: The development of e-courses and modules for dental CPD is an endeavour undertaken by a group of professionals. It must be underpinned by sound pedagogical and e-learning principles and must incorporate elements for effective visual learning and visual design and a simple, consistent technology.

International peer review in undergraduate dentistry: enhancing reflective practice in an online community of practice.

To stimulate and enhance student learning in the areas of global citizenship, critical reflection and e-learning, an online international peer review using a purpose-built web platform, has been developed between international dental schools. Since its inception in 2007, n = 6 dental schools from six different countries have participated with n = 384 dental students engaged in online peer review. Project development was conceptually analysed utilising Lave and Wenger's notion of a community of practice (CoP). Analysis drew on the three core components within the CoP organising framework: domain, community and practice. All three components were evident in building project identity. The domain focused on both curriculum and institutional co-operation. The community was evident for both educators and students. Finally, analysis of practice was found to be significant in terms of sustained interaction and collaboration. Empirical evaluation is recommended as the next phase of project design.

4,5-diarylisoxazole Hsp90 chaperone inhibitors: potential therapeutic agents for the treatment of cancer.

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by approximately 50%.

Assessment of the neurogenic flare response as a measure of nociceptor C fibre function.

A modified method for quantitative measurement of nociceptor C fibre function is described. The electrophoresis of acetylcholine stimulates C fibres to produce an axon reflex flare which is measured by laser Doppler flowmetry. The use of the dorsal, rather than the plantar, surface of the foot at a skin temperature of 32-33 degrees C rather than 34-35 degrees C improves the sensitivity of the technique. Acetylcholine produces an earlier and more predictable response than normal saline, which is approximately half maximal at a current of 0.2 mA and maximal at 1.0 mA. The use of different current strengths should allow more detailed assessment of neurogenic inflammation and the effects of drugs and disease states on C fibre function.

Migration to the New South Wales North Coast 1986-1991: lifestyle motivated counterurbanisation.

"Some of [Australia's] most rapid population growth rates have been recorded on the North Coast of New South Wales. The paper sets this migration flow in an international context and looks in detail at the profile, decision-making, and experience of 150 households who moved to the North Coast in the 1986-1991 intercensal period. Results corroborate earlier findings that many coastal migrants are motivated by non-economic considerations. ¿Pull' factors are much more important than ¿push' factors, with the influence of the physical environment, climate and relaxed lifestyle dominant."

Direction-finding in humans: ability of individuals to orient towards their place of residence.

The fact that humans have an innate sense of direction is well established. Proof of this skill has usually been demonstrated in experiments in which subjects have been called upon to estimate the direction of the point of origin of a journey. This note extends such work by describing an experiment which showed that blindfolded humans, deprived of environmental cues, also have an ability to estimate accurately the direction of their place of residence within a town, even when driven around that town in such a way as to render tham unable to identify where they are. The experiment throws into question the explanation usually offered for the existence of an innate sense of direction, namely, its value to the species, in an evolutionary sense, in facilitating a return to the starting point of exploratory journeys.

Myogenic microvascular responses are impaired in long-duration type 1 diabetes.

Post-ischaemic hyperaemia is a complex physiological response. Peak flow is predominantly an arteriolar myogenic response, whilst viscoelasticity of supplying arteries determines speed of vasodilatation. Impaired post-ischaemic hyperaemia has been described in neuropathic diabetic feet and might predispose to ulceration. However, the relationships of myogenic response and vasodilatation to diabetic control and microvascular complications are unclear. These relationships were therefore investigated using laser Doppler flowmetry to measure the hyperaemic response on the dorsum of the foot after 10 min ischaemia. Twenty control subjects were compared with 55 long-duration Type 1 diabetic patients in groups of uncomplicated, retinopathic and neuropathic patients. Peak flow (median (interquartile range)) was reduced from 1.40 (1.20-1.61) in control subjects to 1.15 (0.80-1.29), 1.08 (0.75-1.26), and 0.95 (0.62-1.29) arbitrary units in the diabetic groups respectively (p = 0.012-0.004). Time to half peak flow was shorter in neuropathic diabetic patients compared with all other groups: 9.5 (7-19), 14.5 (5-25), 12.5 (6-20), and 4 (3-6) s, respectively (p = 0.027-0.011). Neuropathic patients also had the steepest initial slope of vasodilatation. Thus, in long-duration diabetic patients, the myogenic peak post-ischaemic hyperaemic response is impaired, but this impairment is not specifically associated with microvascular complications and was not related to recent blood glucose control. The shortened time to half peak flow and rapid vasodilatation in neuropathic patients is likely to reflect increased rigidity of their arteries.

Evidence for an abnormal peripherally mediated vascular response to temperature in Raynaud's phenomenon.

It is unclear whether an abnormal vascular response to temperature change, independent of central sympathetic control, exists in Raynaud's phenomenon. We investigated this using the hyperaemic response to localized heating of dorsal foot skin, recorded by laser Doppler flowmetry. Fifteen normal adults, nine patients with primary, and seven with secondary Raynaud's phenomenon were studied. On warming, blood flow normally increases gradually at first, followed by rapid vasodilatation at temperatures above 33 degrees C. Normal geometric mean (95% confidence interval) blood flows at 33 degrees C and 36 degrees C were 0.19 (0.16-0.22) and 0.39 (0.29-0.53) arbitrary units respectively. In primary Raynaud's phenomenon, blood flows were 0.53 (0.44-0.62) and 1.07 (0.86-1.35) arbitrary units respectively (P less than 0.01 compared to normal subjects), showing early vasodilatation. Normal women have an intermediate response between men and primary Raynaud's patients. Responses in secondary Raynaud's phenomenon widely overlap the other groups. We conclude that an abnormal peripheral vascular response to temperature change exists in primary Raynaud's phenomenon.

Reactive hyperaemia in skin of the human foot measured by laser Doppler flowmetry: effects of duration of ischaemia and local heating.

The effect of duration of ischaemia and of local heating on reactive hyperaemia in dorsal foot skin was determined in normal subjects using laser Doppler flowmetry. In the nine subjects studied, peak post-ischaemic blood flow continued to increase significantly with up to 10 min ischaemia and mean peak response was positively correlated with duration of ischaemia (r = 0.997, p less than 0.0002). This is in contrast to whole limb plethysmographic studies which have reported maximal peak flow responses after 3-5 min arterial occlusion. Resting blood flow was found to increase rapidly at skin temperatures above 33 degrees C. In ten subjects, local conductive heating from a median (range) skin temperature of 29.8(26.5-31.0) to 32.5(32.2-33.1) degrees C increased peak flow response after 4 min ischaemia from a mean (95% confidence interval) of 0.778(0.630-0.926) to 0.965(0.788-1.142) arbitrary units, p less than 0.001. The time course of the hyperaemic response was not altered. Local skin warming reduced the within subject coefficient of variation for peak response, calculated from 10 paired recordings, in two out of three subjects. These results show that the duration of ischaemia required to produce a maximal post-ischaemic peak flow response is longer for foot skin than for the whole limb and are consistent with temperature differences being the cause of this. A standard skin temperature (32-33 degrees C) may be useful for studying cutaneous blood flow responses.

Early loss of neurogenic inflammation in the human diabetic foot.

1. Neurogenic inflammation, mediated by nociceptor C fibres, is part of the acute neurovascular response to injury producing the axon reflex flare. Laser Doppler flowmetry was used to measure the flare response induced by the electrophoresis, at various current strengths, of a ring of acetylcholine solution into dorsal foot skin. 2. Nineteen control subjects and 52 long-duration insulin-dependent (Type 1) diabetic patients of similar age (20 without complications; 19 with laser-treated retinopathy; 13 with reduced vibration perception and retinopathy) were studied in order to investigate the possible attenuation of this defence mechanism in diabetes. 3. The maximal (1 mA) flare response [control median (interquartile range): 1.55 (1.16-2.06) arbitrary units] was reduced greatly in neuropathic patients [0.37 (0.24-0.66) arbitrary units; P less than or equal to 0.001 with respect to all other groups], especially those with a previous history of foot ulceration. The flare was also reduced in some patients with retinopathy alone [1.06 (0.56-1.27) arbitrary units; P less than 0.005 with respect to control subjects]. 4. No rightward shift of the curve of hyperaemic response plotted against current strength was found, suggesting that the abnormal response was due to axonal loss rather than to dysfunction. 5. Neurogenic inflammation, mediated by small pain fibres, was markedly impaired in a group of diabetic patients at risk of foot ulceration. Furthermore, impairment of this nociceptor C fibre response can develop before clinical large-fibre neuropathy and could itself predispose to foot complications.

Startin's pneumatic inhaler.

This apparatus was seen by one of us (DAW) in a private collection. Although it was one of the first ether inhalers to be manufactured commercially, and was described in the medical literature of the time, it is not mentioned in any of the histories of anaesthesia. Its genesis was unusual, and it presents a number of interesting features, not least being the purpose for which it was originally designed.

An in vitro pharmacological study of the human trigone--a site of non-adrenergic, non-cholinergic neurotransmission.

Muscle strips from the human detrusor and trigone were studied in vitro. The detrusor muscle contracted strongly to both cholinergic receptor stimulation with carbachol and to electrical field stimulation. There was no evidence of atropine resistance in the detrusor strips. The superficial trigone responded maximally to alpha-adrenergic receptor stimulation but also produced a significant cholinergic response. Intramural nerve stimulation in the presence of both atropine and phentolamine produced a residual non-adrenergic, non-cholinergic (NANC) response of 40% of its maximum at 5 Hz. Electrical stimulation, particularly at the lower frequencies of stimulation, produced relaxation responses in 40% of the superficial trigonal muscle strips. These relaxations were not blocked by atropine, phentolamine or propranolol, but were abolished by tetrodotoxin. The possible role of the cholinergic "input" to the superficial trigone and the importance of the NANC excitatory and inhibitory innervation in preventing vesico-ureteric reflux and and in aiding bladder neck opening is discussed.