Oral health students' perceptions of the learning environment in Australia and New Zealand: A DREEM study.

INTRODUCTION: Oral Health Therapists (OHTs) are a growing workforce globally, with skills in oral health prevention, treatment planning and management of disease. These professionals receive their training through a three-year undergraduate program which leads to the Bachelor of Oral Health degree in Australia and New Zealand. The aim of this study was to describe the learning environment for OHT students in Australia and New Zealand. OHT students were requested to complete the Dundee Ready Education Environment Measure (DREEM) to indicate their perceptions of the environment of their educational program. MATERIALS AND METHODS: Bachelor of Oral Health students from 10 universities in Australia and New Zealand were invited to participate in the survey. The analysis of the students' experiences focused on five domains of educational environment: learning, teaching, academic self-perception, atmosphere and social self-perception. Total DREEM scores were compared to previously published literature for other health professions students. RESULTS: A total of 336 OHT students completed the study, which represented 30% of all OHT students enrolled in the 10 participating universities. Using the DREEM, participants perception of the environment was more positive than negative with an average DREEM total score of 141 (70.5%) out of a maximum score of 200. The model demonstrates university region to be a major predictor in the overall DREEM score, with regional universities scoring higher than urban universities (p = .012). CONCLUSIONS: The DREEM was used to describe OHT students perceptions of the learning environment in Australia and New Zealand. This study found that the university region is a significant predictor of positive experiences for OHT students. By identifying the strengths and weaknesses of contemporary Oral Health programs, this study offers insights into future improvements.

Reliable consultant level data from an Acute Medical Unit: a powerful tool for improvement.

The development of a novel database interrogating the patient management system in the Acute Medical Unit at Forth Valley Royal Hospital, Scotland, has allowed, for the first time, acquisition of reliable individual consultant-level process and outcome data over a 2-year period. These data have a number of uses, including understanding the level of variation between consultant physicians in AMU across key indicators, such as direct discharge percentage (67.5-44.3%), and readmission percentage (4.0-6.8%). Looking at overnight admissions only effectively excluded case mix as a confounder to identify variation in 30-day mortality (0-2.8%). This has allowed benchmarking, and exploring of relationships between volume of work, physician experience, and patient outcomes. For example, no significant relationship was seen between direct discharge percentage and readmission percentage. Furthermore it is extremely useful for individual clinician appraisal and governance. Finally it has practical uses when designing consultant rotas in order to minimise system variation. A key consideration throughout this work has been clear provenance and local clinical ownership of these data, unlike centrally generated data that may not accurately reflect Acute Medical Unit activity.

Resin Infiltration of Caries in Primary Molars in a Community Setting: 24-Month Randomized Controlled Trial Findings.

This study aimed to assess whether resin infiltration of primary molar proximal lesions is more effective than noninvasive measures in radiographically controlling carious lesion progression into the dentin. A split-mouth randomized controlled trial included 90 children, each with 2 proximal lesions confined to the inner half of the enamel or ≤0.5 mm into the dentin. For each child, lesions were randomly allocated to test (infiltration: DMG Icon preproduct and fluoride varnish) or control (fluoride varnish) status. The primary outcome measure was 24-mo radiographic lesion progression. Placement of a restoration during the study period was counted as lesion progression. Proportions of teeth with progressed lesions were compared using the McNemar test. Children also reported on the treatment's acceptability to them. Children (46% female) ranged in age from 6 to 9 y. Their mean number of decayed, missing, and filled teeth (d3mft) was 2.8 (SD 2.6). At baseline, 58% and 42% of children were at moderate and low risk, respectively. Test and control lesions presented with similar radiographic lesions at baseline. At the 24-mo follow-up, 6 children had moved and 30 teeth had exfoliated. In the test and control groups, 15 of 66 lesions (22.7%) and 30 of 69 lesions (43.5%) had progressed, respectively (P < 0.05). The 2-y therapeutic effect (based on pairwise radiographic readings) of infiltration over fluoride varnish was 20.8% (95% confidence interval, 10.6%-30.2%). Nearly all children (96.7%) had enjoyed their visit to the clinic, and more than two-thirds (72.2%) were not worried about returning for treatment. Infiltration is more efficacious than fluoride varnish for controlling carious lesion progression in proximal lesions in primary molars, and most children find the treatment acceptable (Australian New Zealand Clinical Trials Registry ANZCTR.org.au ACTRN12611000827932). Knowledge Transfer Statement: These study findings can help clinicians decide which caries management approach they wish to use to prevent progression of proximal lesions in primary molars. With consideration of cost and patient preference, this information could lead to more appropriate therapeutic decisions.

Impact of a new daily rapid access medical clinic in a Scottish district general hospital.

BACKGROUND: Medical admissions to hospital in the UK are rising by approximately 10% per year. A Medical Assessment Unit (MAU) was opened to help deal with the rising influx of patients. The objectives of this study were to determine if a daily rapid access medical clinic could provide a safe alternative to hospital admission and aid safe discharge for medical patients. METHODS: The rapid access clinic was embedded within the MAU, utilising existing resources. Patients were allocated and reviewed by a senior acute medicine specialist registrar (SpR). Data were collected from January to September 2008. RESULTS: 74 patients seen in the clinic were analysed. 93% of these were managed in an ambulatory fashion, avoiding admission and saving a potential 280 bed days. The same day discharge rate of all patients seen and assessed in the MAU was increased from 17% to 26% (p<0.001), following institution of the clinic. The readmission rate fell from 8% to 4% (p=0.12). CONCLUSIONS: A daily rapid access medical clinic embedded within a MAU was piloted and allowed the safe management of a variety of medical complaints in an ambulatory fashion. It enabled an increase in the discharge rate of patients referred for admission by general practitioners. This seemed to be more robust than as evidenced previously by a trend towards lower readmission rates. These results were dependent on the presence of a senior clinical decision maker to facilitate safe discharges.

Improvement in time to treatment following establishment of a dedicated medical admissions unit.

The importance of medical admissions units (MAU) has been emphasised by the royal colleges and the Society for Acute Medicine. This study looked at the time to treatment of four common medical conditions before and after the establishment of a dedicated MAU. Before the development of the MAU, treatment given in the emergency department (ED; median 111 minutes) was significantly quicker than on the admitting general medical ward (median 262 minutes, p<0.001). Following the establishment of the MAU, treatment given in the ED (median 70 minutes) remained significantly quicker than on the MAU (median 180 minutes, p<0.05). Treatment was given significantly quicker on the MAU compared with the antecedent admitting medical wards (p<0.05). In addition, more patients were treated within protocol-driven time guidelines. In summary, the establishment of a MAU significantly improved time to treatment, compared with admitting directly to general medical wards. This has implications for patients who are boarded directly to medical wards when the MAU is at full capacity.

Improvement in out-of-hours outcomes following the implementation of Hospital at Night.

BACKGROUND: Hospital at Night (H@N) is a Department of Health (England) driven programme being widely implemented across UK. It aims to redefine how medical cover is provided in hospitals during the out-of-hours period. AIM: To investigate whether the implementation of H@N is associated with significant change in system or clinical outcomes. DESIGN: An observational study for 14 consecutive nights before, and 14 consecutive nights after the implementation of H@N. Data were collected from the Combined surgical and medical Assessment Unit (CAU), the 18 medical/surgical wards (The Ward Arc) and the four High Dependency Units (The Critical Care corridor) within the Royal Infirmary of Edinburgh. METHODS: Following an overnight episode of clinical concern, data were gathered on response time, seniority of reviewing staff, patient outcome and the use of Standardized Early Warning Score (SEWS). RESULTS: Two hundred and nine episodes of clinical concern were recorded before the implementation of H@N and 216 episodes afterwards. There was no significant change in response time in the CAU, Ward Arc or Critical Care corridor. However, significant inter-speciality differences in response time were eradicated, particularly in the Critical Care corridor. Following the implementation of H@N, patients were reviewed more frequently by senior medical staff in CAU (28% vs. 4%, P < 0.05) and the Critical Care corridor (50% vs. 22%, P < 0.001). Finally there was a reduction in adverse outcome (defined as unplanned transfer to critical care/cardiac arrest) in the Ward Arc and CAU from 17% to 6% of patients reviewed overnight (P < 0.01). SEWS was more frequently and accurately recorded in CAU. CONCLUSION: This is the first study that we are aware of directly comparing out-of-hours performance before and after the implementation of H@N. Significant improvements in both patient and system outcomes were observed, with no adverse effects noted.

Non-infectious manifestations of stem cell transplantation.

Stem cell transplantation (SCT) is now commonplace within medical practice. With growth in transplant activities, outcomes are likely to continue to improve. Increasing numbers of the population now face life after transplantation. The aetiology of post transplant complications is multifactorial. Background knowledge of SCT and common, radiographically detectable, non-infective complications are important in everyday clinical practice. A review of these complications using a variety of imaging modalities is presented and the process of SCT briefly described. Tumour recurrence is outside the remit of this review.

Competing protein:protein interactions are proposed to control the biological switch of the E coli biotin repressor.

A model is suggested for the complex between the biotin repressor of Escherichia coli, BirA, and BCCP, the biotin carboxyl carrier protein to which BirA transfers biotin. The model is consistent with prior physical and biochemical studies. Measurement of transfer rates for variants of BirA with single-site mutations in the proposed BirA:BCCP interface region also provides support. The unique feature of the proposed interaction between BirA and BCCP is that it uses the same beta-sheet region on the surface of BirA that the protein uses for homodimerization into a form competent to bind DNA. The resulting mutually exclusive protein:protein interfaces explain the novel feature of the BirA regulatory system, namely, that transcription of the genes involved in biotin synthesis is not determined by the level of biotin, per se, but by the level of unmodified BCCP. The model also provides a role for the C-terminal domain of BirA that is structurally similar to an SH3 domain.

Corepressor-induced organization and assembly of the biotin repressor: a model for allosteric activation of a transcriptional regulator.

The Escherichia coli biotin repressor binds to the biotin operator to repress transcription of the biotin biosynthetic operon. In this work, a structure determined by x-ray crystallography of a complex of the repressor bound to biotin, which also functions as an activator of DNA binding by the biotin repressor (BirA), is described. In contrast to the monomeric aporepressor, the complex is dimeric with an interface composed in part of an extended beta-sheet. Model building, coupled with biochemical data, suggests that this is the dimeric form of BirA that binds DNA. Segments of three surface loops that are disordered in the aporepressor structure are located in the interface region of the dimer and exhibit greater order than was observed in the aporepressor structure. The results suggest that the corepressor of BirA causes a disorder-to-order transition that is a prerequisite to repressor dimerization and DNA binding.

Reduced-scale large-zone analytical gel-filtration chromatography for measurement of protein association equilibria.

The proteasome plays a central role in eukaryotic cells since it is responsible for the degradation of specific proteins involved in a large range of cellular processes. Analysis of proteasome mechanisms of action, or in vitro reconstitution, or dissection of the complex biological pathways in which it partakes, requires a reliable source of pure active proteasome. Although the biologically relevant form of the proteasome is usually considered to be the 26S proteasome, this unit describes different methods for purification and study of both 26S and 20S proteasomes from Saccharomyces cerevisiae cells.

Regulated assembly of transcription factors and control of transcription initiation.

Proteins that function in regulation of transcription initiation are typically homo or hetero-oligomeric. Results of recent biophysical studies of transcription regulators indicate that the assembly of these proteins is often subject to regulation. This regulation of assembly dictates the frequency of transcription initiation via its influence on the affinity of a transcription regulator for DNA and its affect on target site selection. Factors that modulate transcription factor assembly include binding of small molecules, post-translational modification, DNA binding and interactions with other proteins. Here, the results of recent structural and/or thermodynamic studies of a number of transcription regulators that are subject to regulated assembly are reviewed. The accumulated data indicate that this phenomenon is ubiquitous and that mechanisms utilized in eukaryotes and prokaryotes share common features.

Multiple disordered loops function in corepressor-induced dimerization of the biotin repressor.

Cooperative association of the Escherichia coli biotin repressor with the biotin operator is allosterically activated by binding of the corepressor, bio-5'-AMP. The corepressor function of the adenylate is due, in part, to its ability to induce repressor dimerization. Since a high-resolution structure of only the apo or unliganded repressor is currently available, the location of the dimerization interface on the protein structure is not known. Here, five mutants in the corepressor-binding domain of the repressor have been analyzed with respect to their DNA-binding and self-assembly properties. Results of these studies reveal that four of the mutant proteins exhibit defects in DNA binding. These same proteins are compromised in self-assembly. Furthermore, in the three-dimensional structure of the apo protein the mutations all lie in partially disordered surface loops, one of which is known to participate directly in corepressor binding. These results suggest that multiple disordered surface loops function in the corepressor-induced dimerization required for sequence-specific DNA binding by the biotin repressor.

Function of a conserved sequence motif in biotin holoenzyme synthetases.

The biotin holoenzyme synthetases (BHS) are essential enzymes in all organisms that catalyze post-translational linkage of biotin to biotin-dependent carboxylases. The primary sequences of a large number of these enzymes are now available and homologies are found among all. The glycine-rich sequence, GRGRXG, constitutes one of the homologous regions in these enzymes and, based on its similarity to sequences found in a number of mononucleotide binding enzymes, has been proposed to function in ATP binding in the BHSs. In the Escherichia coli enzyme, the only member of the family for which a three-dimensional structure has been determined, the conserved sequence is found in a partially disordered surface loop. Mutations in the sequence have previously been isolated and characterized in vivo. In this work these single-site mutants, G115S, R118G, and R119W, of the E. coli BHS have been purified and biochemically characterized with respect to binding of small molecule substrates and the intermediate in the biotinylation reaction. Results of this characterization indicate that, rather than functioning in ATP binding, this glycine-rich sequence is required for binding the substrate biotin and the intermediate in the biotinylation reaction, biotinyl-5'-AMP. These results are of general significance for understanding structure-function relationships in biotin holoenzyme synthetases.

Dimerization of the Escherichia coli biotin repressor: corepressor function in protein assembly.

The repressor of biotin biosynthesis binds to the biotin operator sequence to repress transcription initiation at the biotin biosynthetic operon. Site-specific binding of BirA to the biotin operator is allosterically regulated by binding of the small molecule, biotinyl-5'-adenylate (bio-5'-AMP). The operator is a 40 base pair imperfect inverted palindrome and two holorepressor monomers bind cooperatively to the two operator half-sites. Results of previous detailed analyses of binding of holoBirA to bioO indicate that site-specific DNA binding and protein dimerization are obligatorily linked in the system. In the present work equilibrium sedimentation measurements have been used to examine the assembly properties of the aporepressor and its complexes with small ligands biotin and bio-5'-AMP. Results of these measurements indicate that while the free protein and the biotin complex exhibit no tendency to self-associate, the adenylate-bound protein assembles into dimers with an equilibrium constant of 11 microM. The results suggest that one mechanism by which the adenylate promotes binding of BirA to the biotin operator is by promoting repressor dimerization.

Ligand-linked structural changes in the Escherichia coli biotin repressor: the significance of surface loops for binding and allostery.

The Escherichia coli repressor of biotin biosynthesis (BirA) is an allosteric site-specific DNA-binding protein. BirA catalyzes synthesis of biotinyl-5'-AMP from substrates biotin and ATP and the adenylate serves as the positive allosteric effector in binding of the repressor to the biotin operator sequence. Although a three-dimensional structure of the apo-repressor has been determined by X-ray crystallographic techniques, no structures of any ligand-bound forms of the repressor are yet available. Results of previously published solution studies are consistent with the occurrence of conformational changes in the protein concomitant with ligand binding. In this work the hydroxyl radical footprinting technique has been used to probe changes in reactivity of the peptide backbone of BirA that accompany ligand binding. Results of these studies indicate that binding of biotin to the protein results in protection of regions of the central domain in the vicinity of the active site and the C-terminal domain from chemical cleavage. Biotin-linked changes in reactivity constitute a subset of those linked to adenylate binding. Binding of both bio-5'-AMP and biotin operator DNA suppresses cleavage at additional sites in the amino and carboxy-terminal domains of the protein. Varying degrees of protection of the five surface loops on BirA from hydroxyl radical-mediated cleavage are observed in all complexes. These results implicate the C-terminal domain of BirA, for which no function has previously been known, in small ligand and site-specific DNA binding and highlight the significance of surface loops, some of which are disordered in the apoBirA structure, for ligand binding and transmission of allosteric information in the protein.

Potent anti-hepatitis B viral activity and inhibition of bacteriophage T7 RNA polymerase by a "fat" nucleoside and its 5'-triphosphate derivative: synthetic, biochemical, and biological studies of 4,8-diamino-6-imino-6H-1-beta-D-ribofuranosyl-imidazo[4,5-E] [1,3]diazepine-5'-triphosphate.

The title nucleoside, 4,8-diamino-6-imino-6H-1-beta-d-ribofuranosylimidazo[4,5-e][1,3]-d iazepine, exhibited potent anti-hepatitis B viral activity with minimum toxicity in vitro, and its 5'-triphosphate derivative strongly inhibited the bacteriophage T7 RNA polymerase.

A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation.

The Escherichia coli biotin holoenzyme synthetase, BirA, catalyzes transfer of biotin to the epsilon amino group of a specific lysine residue of the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase. Sequences of naturally biotinylated substrates are highly conserved across evolutionary boundaries, and cross-species biotinylation has been demonstrated in several systems. To define the minimal substrate requirements in BirA-catalyzed biotinylation, we have measured the kinetics of modification of a 23-residue peptide previously identified by combinatorial methods. Although the sequence of the peptide bears little resemblance to the biotinylated sequence in BCCP, it is enzymatically biotinylated in vivo. Rates of biotin transfer to the 23-residue peptide are similar to those determined for BCCP. To further elucidate the sequence requirements for biotinylation, transient kinetic measurements were performed on a series of amino- and carboxy-terminal truncations of the 23-mer. The results, determined by stopped-flow fluorescence, allowed identification of a 14-residue peptide as the minimum required sequence. Additional support was obtained using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric analysis of peptides that had been incubated with an excess of biotinyl-5'-adenylate intermediate and catalytic amounts of BirA. Results of these measurements indicate that while kinetically inactive truncations showed no significant shift in molecular mass to the values expected for biotinylated species, kinetically active truncations exhibited 100% biotinylation. The specificity constant (k(cat)/Km) governing BirA-catalyzed biotinylation of the 14-mer minimal substrate is similar to that determined for the natural substrate, BCCP. We conclude that the 14-mer peptide efficiently mimics the biotin acceptor function of the much larger protein domain normally recognized by BirA.