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Periodontitis is a site-specific, chronic disease treated by non-surgical debridement of subgingival plaque. We aimed to determine the microbiome of sites that did not respond to this treatment (NR) compared with paired good responding (GR) sites before and after treatment. In a longitudinal cohort study, clinical parameters of disease and biological samples were taken prior to and 3 months after treatment. Twelve NR sites from six participants were paired with GR sites within the same participant. Subgingival plaque samples were subjected to bacterial community analysis using 16S rRNA gene sequencing. There were no significant differences in clinical parameters and microbial communities at baseline between GR and NR sites. Bacterial communities in deep pockets were dominated by a small number of species, notably Porphyromonas gingivalis and Treponema denticola. In NR sites three months after treatment there was no significant change in bacterial composition whilst there was a collapse in the abundance of pathobionts in GR sites. NR sites were not identifiable prior to treatment by clinical or microbiological parameters. Treatment failed to disrupt pathogenic bacterial community in NR sites. Targeted suppression of particular species should be considered to initiate community collapse and aid disease resolution. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the effect of treatment with the saliva biomimetic, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and SnF2 /NaF compared with SnF2 /NaF alone on coronal surface caries progression in head-and-neck cancer patients undergoing radiotherapy.Methods: Twenty-four participants were randomized into two groups. Both groups used 0.4% SnF2 gel and a 0.32% NaF toothpaste; the test group also applied a crème containing 10% CPP-ACP three times daily while the control group used an identical crème without CPP-ACP (placebo). Resting saliva flow rate and saliva fluoride concentrations were determined. Caries status was assessed using ICDASII at baseline and 12-weeks postradiotherapy. Data were statistically analysed using a linear mixed effects model.Results: Both groups showed significantly reduced resting saliva flow rate (P < 0.001) postradiotherapy. There were no significant differences in flow rates and fluoride concentration between groups. The CPP-ACP group exhibited a significant (P < 0.05) 51% reduction in coronal surface caries progression compared with the placebo group.Conclusion: Resting salivary flow rate was significantly reduced in head-and-neck cancer patients following radiotherapy and use of CPP-ACP with SnF2 /NaF significantly lowered caries progression compared with SnF2 /NaF alone. [ABSTRACT FROM AUTHOR]

Background: Interest in the association between oral cancer risk and Candida-associated promotion of mucosal dysplasia continues. However, little is known of the presence and amount of oral yeast in the mouths of healthy patients without mucosal lesions. The purpose of this prospective cross-sectional clinical study was to ascertain the prevalence and degree of carriage of Candida in the oral cavities of a non-cancer population, with reference to a range of parameters affecting the oral environment.Methods: Oral rinse samples were collected from a sample of 203 patients attending the Royal Dental Hospital of Melbourne and analysed for the presence and degree of colonization of yeast species that were phenotypically identified as albicans and non-albicans species.Results: Oral yeast carriage was found in 98/203 patients (48.3%), and of these, 83 (84.7%) patients carried C. albicans. There was no statistical difference in carriage when comparing gender, age, or presence of a removable prosthesis.Conclusions: Both smoking and the presence of active carious lesions were found to be positively correlated with the carriage of oral Candida. Individuals who are current smokers are nearly seven times more likely to have oral Candida, and participants with high candidal colonization are more likely to be current smokers. Participants with active carious lesions were also more likely to carry oral Candida. [ABSTRACT FROM AUTHOR]

Abstract: The linear no-threshold (LNT) model has been the regulatory "law of the land" for decades. Despite the long-standing use of LNT, there is significant ongoing scientific disagreement on the applicability of LNT to low-dose radiation risk. A review of the low-dose risk literature of the last 10 y does not provide a clear answer, but rather the body of literature seems to be split between LNT, non-linear risk functions (e.g., supra- or sub-linear), and hormetic models. Furthermore, recent studies have started to explore whether radiation can play a role in the development of several non-cancer effects, such as heart disease, Parkinson's disease, and diabetes, the mechanisms of which are still being explored. Based on this review, there is insufficient evidence to replace LNT as the regulatory model despite the fact that it contributes to public radiophobia, unpreparedness in radiation emergency response, and extreme cleanup costs both following radiological or nuclear incidents and for routine decommissioning of nuclear power plants. Rather, additional research is needed to further understand the implications of low doses of radiation. The authors present an approach to meaningfully contribute to the science of low-dose research that incorporates machine learning and Edisonian approaches to data analysis., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Objectives: To compare the remineralisation efficacy and ion bioavailability of two novel SnF 2 -containing dentifrices in a blinded, cross-over, randomised in situ clinical study., Methods: Six participants wore removal palatal appliances holding human enamel and dentine blocks with subsurface lesions. Appliances were worn for two treatment periods of 14 consecutive days each, with a one-week washout period in-between. Participants were randomly allocated to rinse with a 1:5 diluted coded slurry of one of two dentifrices containing either 5 % casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) +1100 ppm F as SnF 2 [MIPOP], or 1100 ppm F as SnF 2 [CT], for 1 min, four times a day. Saliva was collected post-treatment and analysed for tin, calcium, inorganic phosphate and fluoride ions using atomic absorption spectrophotometry and ion chromatography. Enamel and dentine lesions were analysed for percent remineralisation (%R) using transverse microradiography and percent surface microhardness recovery (%SMHR)., Results: MIPOP released significantly higher F (3.00 ± 0.27 mM), Ca (15.23 ± 3.23 mM) and Sn (1.18 ± 0.13 mM) into saliva whereas CT released 2.89 ± 0.32 mM F and only 0.84 ± 0.11 mM Ca and 0.28 ± 0.10 mM Sn. MIPOP produced significantly higher %R than CT: 25.6 ± 1.5 % compared to 15.2 ± 0.7 % in enamel, and 33.6 ± 3.1 % compared to 20.6 ± 1.1 % in dentine. Additionally, MIPOP produced significantly higher %SMHR (18.2 ± 7.9 %) compared to CT (4.1 ± 0.6 %)., Conclusions: Both dentifrices promoted remineralisation, but the MIPOP dentifrice with added CPP-ACP and the ion-stabilising effects of CPP released higher amounts of bioavailable tin and produced significantly higher remineralisation and surface microhardness recovery., Clinical Significance: Modern dentifrices contain SnF 2 for a range of oral health benefits. Challenges associated with stability of these formulations can affect ion bioavailability, reducing efficacy. Two dentifrices with SnF 2 promoted remineralisation in situ, however the dentifrice with the added saliva biomimetic CPP-ACP was superior and therefore may produce greater health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Evacuation and relocation are key actions used to protect the public in response to natural or technological disasters, but there are inherent risks to both. Unfortunately, these risks have not been fully quantified, which limits the ability of emergency managers and the public to effectively balance the risks and benefits of evacuation or relocation. This work provides quantitative data on the risks of health effects from displacement following evacuation or relocation., Methods: Researchers performed a literature review and meta-analysis of published studies and quantified risks of 14 different health effects, including both physical and socio-behavioral outcomes, from studies of 9 different disaster types., Results: The findings show statistically significant increases in 9 of the 14 health effects in displaced populations, indicating an increased likelihood of experiencing detrimental health effects compared with nondisplaced populations. A pooled analysis of all negative health effects found an odds ratio of 1.49 (95% confidence interval: 1.24-1.79), which shows a significant relationship between displacement and negative health outcomes., Conclusions: These findings demonstrate that evacuated or relocated populations have an increased risk of experiencing negative health effects associated with displacement. The broad number of disaster types included mean that findings are applicable to any emergency evacuation or relocation.

The human oral microbiome is becoming recognized as playing roles in health and disease well beyond the oral cavity over the lifetime of the individual. The oral microbiome is hypothesized to result from specific colonization events followed by a reproducible and ordered development of complex bacterial communities. Colonization events, proliferation, succession and subsequent community development are dependent on a range of host and environmental factors, most notably the neonate diet. It is now becoming apparent that early childhood and prenatal influences can have long term effects on the development of human oral microbiomes. In this review, the temporal development of the infant human oral microbiome is examined, with the effects of prenatal and postnatal influences and the roles of specific bacteria. Dietary and environmental factors, especially breastfeeding, have a significant influence on the development of the infant oral microbiome. The evidence available regarding the roles and functions of early colonizing bacteria is still limited, and gaps in knowledge where further research is needed to elucidate these specific roles in relation to health and disease still exist.

Background: The current study explored the perspectives of preparedness for dental practice from a range of relevant stakeholders (i.e., educators, employers, final-year students, graduates, practitioners, and professional associations) using an anonymous online survey in which participants described either their preparedness for practice, or the preparedness of graduates they have encountered, across six domains., Results: A total of 120 participants completed the survey. Participants were from several Australian states and territories; regional, rural, and urban locations; and working in the public and private sector. Students and new graduates generally felt prepared for activities in all the identified domains. Stakeholders reported consistently that the knowledge of dental profession graduates was at the required level to enter practice in Australia in a safe way. Activities involving the knowledge of clinical entrepreneurship and financial solvency were the dimensions where students and graduates felt least prepared (e.g., explaining fees, negotiating finances). In the domains involving clinical and technical competencies, students and new graduates self-assessed as less prepared around managing dental trauma and medical emergencies. On the other hand, activities around social and community orientation, and to a lesser extent professional attitudes and ethical judgements, were the dimensions where students and graduates felt the most prepared., Conclusions: Present findings indicate that there appear to be good standards of preparedness for practice for graduate dental professionals. This exploratory study provides insights into the nature of preparedness for Australian dental professionals and provides a basis for targeting education and professional development to address areas of need., (© 2022. The Author(s).)

Background: As part of an evaluation of an oral healthcare practice-based model that identifies patients with prediabetes or type-2 diabetes, this study reports on the proportion of patients identified with clinically confirmed type-2 diabetes (T2D)/prediabetes and barriers of implementation of the model., Methodology: Urban and rural oral healthcare practices were invited to participate. Participating practices invited eligible patients to participate in the screening program using the Australian Type-2 Diabetes Risk Assessment Tool (AUSDRISK). Participants were categorised as low, intermediate, or high-risk for prediabetes/T2D. Patients in the intermediate or high-risk category were referred to their General Medical Practitioner (GP) for further investigation., Results: Fifty-one oral healthcare practices and 76 Oral Health Professionals (OHP) participated (60 Dentists, 8 Dental Hygienists, 8 Oral Health Therapists). 797 patients were screened; 102 were low-risk; 331 intermediate-risk; and 364 high-risk for T2D. Of the 695 participants in the intermediate or high-risk groups, 386 (55.5%) were referred to their GP for T2D assessment. Of them, 96 (25.0%) results were returned to OHPs. Of the returned results, six were (6.3%) diagnosed with pre-T2D., Conclusion: Patients found to have undiagnosed T2D/prediabetes (6.3%) were within the expected range reported in the literature. Findings indicate that identifying individuals at an elevated risk of having or developing T2D is effective, feasible and could be incorporated into oral healthcare settings. However, this integration may require additional OHPs training and education to ensure that patients at elevated risk of T2D are referred for further assessment., (© 2022. The Author(s).)

Background: Human microbiomes assemble in an ordered, reproducible manner yet there is limited information about early colonisation and development of bacterial communities that constitute the oral microbiome., Aim: The aim of this study was to determine the effect of exposure to breastmilk on assembly of the infant oral microbiome during the first 20 months of life., Methods: The oral microbiomes of 39 infants, 13 who were never breastfed and 26 who were breastfed for more than 10 months, from the longitudinal VicGeneration birth cohort study, were determined at four ages. In total, 519 bacterial taxa were identified and quantified in saliva by sequencing the V4 region of the bacterial 16S rRNA genes., Results: There were significant differences in the development of the oral microbiomes of never breastfed and breastfed infants. Bacterial diversity was significantly higher in never breastfed infants at 2 months, due largely to an increased abundance of Veillonella and species from the Bacteroidetes phylum compared with breastfed infants., Conclusion: These differences likely reflect breastmilk playing a prebiotic role in selection of early-colonising, health-associated oral bacteria, such as the Streptococcus mitis group. The microbiomes of both groups became more heterogenous following the introduction of solid foods., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: As part of a larger study on the identification of undiagnosed Type 2 diabetes (T2D), and prediabetes patients in dental settings, this study explored oral healthcare professionals' (OHP) attitudes with respect to the relevance and appropriateness of screening for prediabetes/T2D in general oral healthcare settings. It also aims to gain a deeper understanding of OHPs' concerns and perceived barriers to screening for T2D., Methods: Semi-structured interviews were conducted with 11 OHPs: eight dentists, two dental hygienists and one oral health therapist. Interviews were audio recorded, transcribed verbatim and analysed using thematic analysis., Results: Themes that emerged from the interviews were organised under three major categories: 1) Implementation: OHPs willingness to screen for prediabetes/T2D; 2) Barriers to implementation of screenings; subdivided into: a) lack of knowledge and formal training about T2D screening methodology; b) concerns about patients' awareness and acceptance of T2D screening in oral healthcare settings; c) costs and reimbursement for the time and resources required to screen patients; and d) legal and scope of practice; and 3) Collaboration and communication between OHPs and General practitioners (GP)., Conclusions: The oral healthcare setting was considered as appropriate for medical screening, and OHPs were willing to participate in screening for prediabetes/T2D. Nonetheless, for the successful implementation of a screening programme, several barriers need to be addressed, and effective medical screening would require collaboration between oral health and medical and other health professionals, as well as clarification of legal and reimbursement issues., (© 2021. The Author(s).)

Background: For reasons unclear, some stored red blood cells (RBCs) have low hemolysis, while others have high hemolysis, which impacts quality consistency. To identify variables that influence hemolysis, routine quality control (QC) data for 42-days-stored RBCs with corresponding donor information were analyzed., Study Design and Methods: RBC QC and donor data were obtained from a national blood supplier. Regression models and analyses were performed on total cohort stratified by donor sex and by high hemolysis (≥90th percentile) vs control (<90th percentile) samples, including matching., Results: Data included 1734 leukoreduced RBCs (822 female, 912 male), processed by buffy coat-poor or whole blood filtration methods. Male RBCs had larger volume, hemoglobin content, and higher hemolysis than female RBCs (median hemolysis, 0.24% vs 0.21%; all P < .0001). Multivariable regression identified increased body mass index (BMI) and RBC variables were associated with higher hemolysis (P < .0001), along with older female age and buffy coat-poor processing method (P < .002). Logistic regression models comparing the high and control hemolysis subsets, matched for RBC component variables and processing method, identified overweight-obese BMI (>27 kg/m 2 ) in males remained the single donor-related variable associated with higher hemolysis (P < .0001); odds ratio, 3 (95% confidence interval [CI], 1.3-6.7), increasing to 4 (95% CI, 1.8-8.6) for obese males (BMI > 30 kg/m 2 ). Female donor obesity and older age trended toward higher hemolysis., Conclusion: Donor BMI, sex, and female age influence the level of hemolysis of 42-days-stored RBCs. Other factors, not identified in this study, also influence the level of hemolysis., (© 2020 AABB.)

This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 Å. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 Å with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.

Background: Clinical trials and laboratory studies from around the world have shown that GC Tooth Mousse Plus ® (TMP) is effective in protecting teeth from tooth decay and erosion, buffering dental plaque pH, remineralising white spot lesions and reducing dentine hypersensitivity. However, no other study has assessed the experiences of oral health, before, during and after individuals becoming regular users of TMP. The aim of this study was to identify how participants' oral health status changed after introducing TMP into their oral hygiene routine., Methods: A qualitative study using Charmaz's grounded theory methodology was conducted. Fifteen purposively sampled regular users of TMP were interviewed. Transcripts were analysed after each interview. Data analysis consisted of transcript coding, detailed memo writing, and data interpretation., Results: Participants described their experiences of oral health and disease, before, during and after introducing TMP into their daily oral hygiene routine, together with the historical, biological, financial, psychosocial, and habitual dimensions of their experiences. Before becoming a regular user of TMP, participants described themselves as having a damaged mouth with vulnerable teeth, dry mouth, and sensitivity. Various aspects of participants' histories were relevant, such as, family history and history of oral disease. Having a damaged mouth with vulnerable teeth, dry mouth and sensitivity was explained by those elements. Despite some initial barriers, once being prescribed TMP by a dental professional, a three-fold process of change was initiated: starting a new oral hygiene routine, persevering daily, and experiencing reinforcing outcomes. This process led to a fundamental lifestyle change. Participants transitioned from having a damaged mouth with vulnerable teeth to having a comfortable mouth with strong teeth; at the same time participants felt empowered by this newly found status of being able to keep their teeth for life. Barriers and facilitators for incorporating TMP on daily oral hygiene routine were also identified., Conclusions: Participants valued having a comfortable mouth with strong teeth, which did not require repeated restorations. Seeing concrete results in their mouths and experiencing a more comfortable mouth boosted adherence to daily applications of TMP, which was maintained over time.

Aroma compounds are diverse low molecular weight organic molecules responsible for the flavour of food, medicines or cosmetics. Natural and artificial aroma compounds are manufactured and used by the industry to enhance the flavour and fragrance of products. While the low concentrations of aroma compounds present in food may leave no effect on the structural integrity of the mucosa, the effect of concentrated aroma volatiles is not well understood. At high concentrations, like those found in some flavoured products such as e-cigarettes, some aroma compounds are suggested to elicit a certain degree of change in the mucin glycoprotein network, depending on their functional group. These effects are particularly associated with carbonyl compounds such as aldehydes and ketones, but also phenols which may interact with mucin and other glycoproteins through other interaction mechanisms. This study demonstrates the formation of such interactions in vitro through the use of molecular hydrodynamics. Sedimentation velocity studies reveal that the strength of the carbonyl compound interaction is influenced by compound hydrophobicity, in which the more reactive short chain compounds show the largest increase in mucin-aroma sedimentation coefficients. By contrast, the presence of groups that increases the steric hindrance of the carbonyl group, such as ketones, produced a milder effect. The interaction effects were further demonstrated for hexanal using size exclusion chromatography light scattering (SEC-MALS) and intrinsic viscosity. In addition, phenolic aroma compounds were identified to reduce the sedimentation coefficient of mucin, which is consistent with interactions in the non-glycosylated mucin region.

The 6-deoxy-6-aminocelluloses-or "aminocelluloses"-are a class of synthetic natural cellulose derivatives which are mostly aqueous soluble and have excellent film-forming properties. Recent studies have connected these properties at the molecular level with protein-like self-associative behaviour for a range of aminocelluloses including a 6-deoxy-6-(ω-aminoethyl) aminocellulose AEA-1 with the association being a two-stage process-a reversible oligomerisation followed by further (semi-reversible) aggregation into larger structures. Here, we synthesise and compare a new 6-deoxy-6-(ω-aminoethyl) aminocellulose AEA-1' with different degree of substitution with one with further alkyl derivatisation, namely 6-deoxy-6-(ω-hydroxyethyl) aminocellulose HEA-1'. As with AEA-1, sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge still show a two-stage process for both AEA-1' and HEA-1', with the latter giving higher molar masses. The consequences of these properties for use as consolidants for archaeological wood are considered.

Cucurbits are plants that have been used frequently as functional foods. This study includes the extraction, isolation, and characterisation of the mesocarp polysaccharide of Cucurbita moschata . The polysaccharide component was purified by gel filtration into three fractions (NJBTF1, NJBTF2, and NJBTF3) of different molecular weights. Characterisation includes the hydrodynamic properties, identification of monosaccharide composition, and bioactivity. Sedimentation velocity also indicated the presence of small amounts of additional discrete higher molecular weight components even after fractionation. Sedimentation equilibrium revealed respective weight average molecular weights of 90, 31, and 19 kDa, with the higher fractions (NJBTF1 and NJBTF2) indicating a tendency to self-associate. Based on the limited amount of data (combinations of 3 sets of viscosity and sedimentation data corresponding to the 3 fractions), HYDFIT indicates an extended, semi-flexible coil conformation. Of all the fractions obtained, NJBTF1 showed the highest bioactivity. All fractions contained galacturonic acid and variable amounts of neutral sugars. To probe further, the extent of glycosidic linkages in NJBTF1 was estimated using gas chromatography-mass spectrometry (GCMS), yielding a high galacturonic acid content (for pectin polysaccharide) and the presence of fructans-the first evidence of fructans (levan) in the mesocarp. Our understanding of the size and structural flexibility together with the high bioactivity suggests that the polysaccharide obtained from C. moschata has the potential to be developed into a therapeutic agent.

Polycaprolactone (PCL) is a synthetic polymer with good mechanical properties that are useful to produce biomaterials of clinical application. It can be successfully combined with chitosan, which enhances the biomaterial properties through the modulation of molecular and cellular mechanisms. The objective of this study was to evaluate the effects of the use of electrospun fibrous membranes consisting of polycaprolactone (PCL) or polycaprolactone coated with chitosan and poly(ethylene oxide) (PCL+CHI/PEO) on mouse skin lesions. Sixty four Black-57 mice were divided into PCL and PCL+CHI/PEO groups. A 1 cm 2 lesion was made on the animals' backs, and the membranes were sutured in place. The tissues were extracted on the 3rd, 7th, and 14th days after the lesion. The tissues were analyzed by histology with Hematoxylin and Eosin (H&E) and Sirius Red stains, morphometry, immunohistochemistry, and Western blot. On the 3rd, 6th, and 9th days after the lesion, the PCL+CHI/PEO group showed a higher wound-healing rate (WHR). On the 3 day, the PCL+CHI/PEO group showed a greater amount of inflammatory infiltrate, greater expression of proliferating cell nuclear antigen (PCNA), and smooth muscle actin (α-SMA) ( p < 0.05) compared to the PCL group. On the 7th day after the lesion, the PCL+CHI/PEO group showed a greater amount of inflammatory infiltrate, expression of Tumor Necrosis Factor (TNF-α) and PCNA ( p < 0.05). In addition, it showed a greater immunolabeling of Monocyte Chemoattractant Protein-1 (MCP-1) and deposition of collagen fibers compared to the PCL group. The PCL+CHI/PEO membrane modulated the increase in the inflammatory infiltrate, the expression of MCP-1, PCNA, and α-SMA in lesions of mice.

Purpose: Insulin, in typical use, undergoes multiple changes in temperature; from refrigerator, to room temperature, to body temperature. Although long-term storage temperature has been well-studied, the short term changes to insulin are yet to be determined. Insulin detemir (IDet) is a clinically available, slow-acting, synthetic analogue characterised by the conjugation of a C14 fatty acid. The function of this modification is to cause the insulin to form multi-hexameric species, thus retarding the pharmacokinetic rate of action. In this investigation, the temperature dependence properties of this synthetic analogue is probed, as well as expiration., Methods: Dynamic light scattering (DLS) and viscometry were employed to assess the effect of temperature upon IDet. Mass spectrometry was also used to probe the impact of shelf-life and the presence of certain excipients., Results: IDet was compared with eight other insulins, including human recombinant, three fast-acting analogues and two other slow-acting analogues. Of all nine insulins, IDet was the only analogue to show temperature dependent behaviour, between 20 °C and 37 °C, when probed with non-invasive backscatter dynamic light scattering. Upon further investigation, IDet observed significant changes in size related to temperature, direction of temperature (heated/cooled) and expiration with cross-correlation observed amongst all 4 parameters., Conclusions: These findings are critical to our understanding of the behaviour of this particular clinically relevant drug, as it will allow the development of future generations of peptide-based therapies with greater clinical efficacy., Competing Interests: Declaration of Competing Interest R.B.G. and S.I.J. are funded by IDDT. G.G.A. is a non-executive director of IDDT. No other authors express any competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose Ocular motility disturbances following retinal detachment surgery are well documented, resulting in ocular misalignment and disabling diplopia. Interestingly, there has been a downward trend over the last decade across the United Kingdom with the evolution of refined vitrectomy techniques and instrumentation. We aim to report our updated experience on factors influencing botulinum toxin outcomes in view of the trend toward vitrectomy. Methods The Moorfields strabismus service carried out a follow-up retrospective study of all subjects that received botulinum toxin for retinal surgery-related strabismus at our center over an eleven-year period. All new onset constant or intermittent strabismus following retinal detachment surgery were included. Botulinum toxin response was stratified to good and poor. Results 32 patients fulfilled our criteria, with a mean follow-up of 20 months. The majority were vitrectomised eyes (62%), presented with diplopia (60%) and exotropia (66%). All isolated and combined vertical deviations (18%) were noted among cryobuckled eyes only. Baseline largest mean horizontal deviation was 49 and 51 prism diopters (PD) among the good and poor responders, respectively. A statistically and clinically significant reduction in the horizontal angle of deviation was noted among the good ( p < .0001) responders, requiring a mean of six injections, in comparison to the poor responders ( p = .03). Of the good responders, five patients (16%) with decompensated phorias regained fusion control. A small number of complications (15%) were noted, the most marked being intractable diplopia in a good responder (3%) with failure to fuse. Conclusions Botulinum toxin is a useful treatment modality, particularly when surgical options are limited. It can restore binocularity in patients with preexisting fusion potential. Ocular cosmesis can be achieved but requires ongoing injections. Barriers to fusion restoration include multiple retinal surgeries, persistent macula pathology and central-peripheral retinal rivalry. This highlights the need for rigorous baseline macula assessment to allow a tailored approach when considering botulinum toxin therapy for strabismus.

Scleroglucan, a neutral β(1-3) glucan with β(1-6) glucan branches every third residue, is being considered as an alternative rod-like, shear thinning high molecular weight β-glucan based polysaccharide to xanthan gum for the management of patients with oropharyngeal dysphagia. It is therefore important to understand more fully its hydrodynamic properties in solution, in particular heterogeneity, molecular weight distribution and its behaviour in the presence of mucin glycoproteins. A commercially purified scleroglucan preparation produced by fermentation of the filamentous fungus Sclerotium rolfsii was analysed in deionised distilled water with 0.02% added azide. Sedimentation velocity in the analytical ultracentrifuge showed the scleroglucan preparation to be unimodal at concentrations >0.75 mg/ml which resolved into two components at lower concentration and with partial reversibility between the components. Sedimentation coefficient versus concentration plots showed significant hydrodynamic non-ideality. Self-association behaviour was confirmed by sedimentation equilibrium experiments with molecular weights between ~3 × 10 6  g/mol to ~5 × 10 6  g/mol after correcting for thermodynamic non-ideality. SEC-MALS-viscosity experiments showed a transition between a rod-shape at lower molar masses to a more flexible structure at higher masses consistent with previous observations. Sedimentation velocity experiments also showed no evidence for potentially problematic interactions with submaxillary mucin., Competing Interests: There are no conflicts of interest., (© 2019 The Authors.)

Protein polysaccharide complexes have been widely studied for multiple industrial applications and are popular due to their biocompatibility. Insulin degludec, an analogue of human insulin, exists as di-hexamer in pharmaceutical formulations and has the potential to form long multi-hexamers in physiological environment, which dissociate into monomers to bind with receptors on the cell membrane. This study involved complexation of two negatively charged bio-polymers xanthan and alginate with clinically-relevant insulin degludec (PIC). The polymeric complexations and interactions were investigated using biophysical methods. Intrinsic viscosity [η] and particle size distribution (PSD) of PIC increased significantly with an increase in temperature, contrary to the individual components indicating possible interactions. [η] trend was X > XA > PIC > A > IDeg. PSD trend was X>A>IDeg>XA>PIC. Zeta (ζ)- potential (with general trend of IDeg < A < XA < X ≈ PIC) revealed stable interaction at lower temperature which gradually changed with an increase in temperature. Likewise, sedimentation velocity indicated stable complexation at lower temperature. With an increase in time and temperature, changes in the number of peaks and area under curve were observed for PIC. Conclusively, stable complexation occurred among the three polymers at 4 °C and 18 °C and the complex dissociated at 37 °C. Therefore, the complex has the potential to be used as a drug delivery vehicle., Competing Interests: The authors declare no conflict of interest.

Vancomycin, a branched tricyclic glycosylated peptide antibiotic, is a last-line defence against serious infections caused by staphylococci, enterococci and other Gram-positive bacteria. Orally-administered vancomycin is the drug of choice to treat pseudomembranous enterocolitis in the gastrointestinal tract. However, the risk of vancomycin-resistant enterococcal infection or colonization is significantly associated with oral vancomycin. Using the powerful matrix-free assay of co-sedimentation analytical ultracentrifugation, reinforced by dynamic light scattering and environmental scanning electron microscopy, and with porcine mucin as the model mucin system, this is the first study to demonstrate strong interactions between vancomycin and gastric and intestinal mucins, resulting in very large aggregates and depletion of macromolecular mucin and occurring at concentrations relevant to oral dosing. In the case of another mucin which has a much lower degree of glycosylation (~60%) - bovine submaxillary mucin - a weaker but still demonstrable interaction is observed. Our demonstration - for the first time - of complexation/depletion interactions for model mucin systems with vancomycin provides the basis for further study on the implications of complexation on glycopeptide transit in humans, antibiotic bioavailability for target inhibition, in situ generation of resistance and future development strategies for absorption of the antibiotic across the mucus barrier.

The use of specially designed wound dressings could be an important alternative to facilitate the healing process of wounds in the hyperglycemic state. Biocompatible dressings combining chitosan and alginate can speed up wound healing by modulating the inflammatory phase, stimulating fibroblast proliferation, and aiding in remodeling phases. However, this biomaterial has not yet been explored in chronic and acute lesions of diabetic patients. The aim of this study was to evaluate the effect of topical treatment with a chitosan-alginate membrane on acute skin wounds of hyperglycemic mice. Diabetes mellitus was induced by streptozotocin (60 mg · kg-1 · day-1 for 5 days, intraperitoneally) and the cutaneous wound was performed by removing the epidermis using a surgical punch. The results showed that after 10 days of treatment the chitosan and alginate membrane (CAM) group exhibited better organization of collagen fibers. High concentrations of interleukin (IL)-1α, IL-1β, granulocyte colony-stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α) were detected in the first and second days of treatment. G-CSF and TNF-α level decreased after 5 days, as well as the concentrations of TNF-α and IL-10 compared with the control group (CG). In this study, the inflammatory phase of cutaneous lesions of hyperglycemic mice was modulated by the use of CAM, mostly regarding the cytokines IL-1α, IL-1β, TNF-α, G-CSF, and IL-10, resulting in better collagen III deposition. However, further studies are needed to better understand the healing stages associated with CAM use.

Objectives: To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study., Materials and Methods: Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model., Results: The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase., Conclusion: This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque., Clinical Significance: Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To reduce animal testing, there is a need to develop novel in-vitro models for evaluating the retention of bioactive compounds in food and pharmaceutical products. Here, a mucus-mimetic platform was developed through a one-step approach based on encapsulating mucin within alginate gel beads. We found that mucins form micron sized aggregates distributed across the surface of the calcium-alginate bead, as shown by environmental scanning electron microscopy (ESEM). Retention of bioactive compounds on the mucin-functionalised surface was tested using a commercial orange drink formulation. To aid flavour retention, different mucoadhesive polymers with varying charge, including anionic, neutral and strongly cationic, were tested for their ability to interact with mucin and aid retaining flavour compounds within the mucin-alginate bead. The alginate-mucin mucus mimic was validated using an ex-vivo bovine tongue, with the flavour retention results showing qualitative agreement. The developed method proved to be a convenient, efficient tool for providing information on the effectiveness of mucoadhesive polymers without variability, safety and sustainability issues associated with an ex-vivo or in-vivo system. We propose that by encapsulating other relevant oral proteins, alongside mucins, current gaps between in-vitro and the ex-vivo systems may be narrowed., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

While a good mucoadhesive biopolymer must adhere to a mucus membrane, it must also have a good unloading ability. Here, we demonstrate that the biopolymer pullulan is partially digested by human salivary α-amylase, thus acting as a controlled release system, in which the enzyme triggers an increased release of flavour. Our oral processing simulations have confirmed an increase in the bioavailability of aroma and salt compounds as a function of oral pullulan degradation, although the release kinetics suggest a rather slow process. One of the greatest challenges in flavour science is to retain and rapidly unload the bioactive aroma and taste compounds in the oral cavity before they are ingested. By developing a cationic pullulan analogue we have, in theory, addressed the "loss through ingestion" issue by facilitating the adhesion of the modified polymer to the oral mucus, to retain more of the flavour in the oral cavity. Dimethylaminoethyl pullulan (DMAE-pullulan) was synthesised for the first time, and shown to bind submaxillary mucin, while still retaining its susceptibility to α-amylase hydrolysis. Although DMAE-pullulan is not currently food grade, we suggest that the synthesis of a sustainable food grade alternative would be a next generation mucoadhesive targeted for the oral cavity., Competing Interests: Competing interestsThe authors declare no competing interests.

Aims and Objectives: To determine the views of nurses and physicians working in intensive care units (ICU) about the aims of glycaemic control and use of their protocols., Background: Evidence about the optimal aims and methods for glycaemic control in ICU is controversial, and current local protocols guiding practice differ between ICUs, both nationally and internationally. The views of professionals on glycaemic control can influence their practice., Design: Cross-sectional, multicentre, survey-based study., Methods: An online short survey was sent to all physicians and nurses of seven ICUs, including questions on effective glycaemic control, treatment of hypoglycaemia and deviations from protocols' instructions. STROBE reporting guidelines were followed., Results: Over half of the 40 respondents opined that a patient spending <75% admission time within the target glycaemic levels constituted poor glycaemic control. Professionals with more than 5 years of experience were more likely to rate a patient spending 50%-74% admission time within target glycaemic levels as poor than less experienced colleagues. Physicians were more likely to rate a patient spending <50% admission time within target as poor than nurses. There was general agreement on how professionals would rate most deviations from their protocols. Nurses were more likely to rate insulin infusions restarted late and incorrect dosage of rescue glucose as major deviations than physicians. Most professionals agreed on when they would treat hypoglycaemia., Conclusions: When surveyed on various aspects of glycaemic control, ICU nurses and physicians often agreed, although there were certain areas of disagreement, in which their profession and level of experience seemed to play a role., Relevance to Clinical Practice: Differing views on glycaemic control amongst professionals may affect their practice and, thus, could lead to health inequalities. Clinical leads and the multidisciplinary ICU team should assess and, if necessary, address these differing opinions., (© 2019 John Wiley & Sons Ltd.)

Rationale, Aims, and Objectives: The practice of glycaemic control of critically ill patients admitted to intensive care units (ICUs) is guided by clinical management protocols, designed locally by the ICUs. These protocols differ significantly in their aims and methods. The aim of this study was to develop a standardized methodology for the systematic and objective analysis and comparison of protocols for glycaemic control implemented in any ICU., Method: The protocols for glycaemic control implemented in seven ICUs of a UK-based ICU network were analysed using techniques of inductive content analysis, through an open coding process and the framework method. This involved the identification and classification of protocol instructions for glycaemic control, as well as of the processes and decisions pertaining to each of these instructions. These were used to develop a framework for the structured and systematic description and comparison of the protocols' contents, and to develop a technique for the protocols' graphic visualization., Results: The following elements were identified or developed: (1) 35 quantifiable variables and 11 non-quantifiable subjects that could be present in an ICU protocol for glycaemic control, to be used as a framework for the description and comparison of contents; (2) a technique for condensing a protocol into a single, comprehensive flowchart; (3) using these flowcharts, a method for assessing the complexity and comprehensiveness of the protocols., Conclusions: The methodology developed in this study will allow for any future work analysing the contents of glycaemic control protocols to be carried out in a structured and standardized way. This may be done either as a standalone study, or as the essential first step in any investigation on the impact of new protocols. In turn, the methodology will facilitate the performance of regional, national, and international comparisons, demonstrating the usefulness of this study at a global scale., (© 2018 John Wiley & Sons, Ltd.)

Submaxillary mucin is a major component that defines the makeup and functionality of saliva. Understanding its structure and function during food intake is key to designing appropriate strategies for enhancing the delivery of flavour. In the present study, the hydrodynamic integrity of bovine submaxillary mucin was characterised under physiological and acidic conditions and it was shown to have a broad molecular weight distribution with species ranging from 100 kDa to over 2000 kDa, and a random coil type of conformation. A decrease in the pH of mucin appeared to result in aggregation and a broader molecular weight distribution, which was shown to correlate with a release of flavour compounds. Our study also provides indications that p -cresol may have an effect on the macromolecular integrity of mucin., Competing Interests: Conflict of InterestThe authors declare no conflict of interest.

Background: Hypoglycemia unawareness (HU) has been attributed to both a downward shift in central nervous system (CNS)-triggered sympatho-adrenal responses to low glycaemic thresholds and a subsequent loss of adrenergic symptoms, which, in addition, to cerebral cortex adaptations permit normal function under hypoglycaemic conditions. Both of these mechanisms are brought about by recurring hypoglycemic events (hypoglycemia-associate autonomic failure, HAAF). This can contribute to repetitive cycles of increasingly severe hypoglycaemia, the consequences of which have considerable impact on relatives and significant others (SO) when providing care to patients with diabetes., Methods: A Systematic Review (SR) of 639 qualitative studies was carried out in accordance with the Preferred Reporting Items for Systematic Review (PRISMA) principles. The search strategy was developed using MeSH terms for a range of electronic databases: CINAHL, Pubmed, EMBASE, Medline, AMED and ASSIA were systematically searched in order to identify a variety of literature relevant to the review topic. Four duplicate studies were removed and a further 630 studies were excluded due to being irrelevant. Five qualitative studies were retained and analysed., Results: The three resultant findings from the literature appraised were i) Experiences and views of Significant Others' (SO) with adult relatives that have HU ii) Support needs of SO and iii) Health professionals interventions to address SO support needs and improve overall HU care. A clear finding was that SO experience difficulties managing HU and this can impact on the relationships that SO and HU patients have. Support needs of SO highlighted were both educational and psychological in nature, with there being a requirement for additional raised awareness within the wider community., Conclusion: It is essential that healthcare professionals offer support, such as teaching and support groups. In addition, providing interventions into improving family knowledge of diabetes and support with regard to psychosocial, behavioural and practical support for the person with diabetes. Moreover, improving resources for families to improve diabetes care. However, as the literature was of a qualitative nature, future recommendations would be quantitative research into these suggested nursing implementations to quantitatively assess their usefulness in practice.

Aims: To evaluate retreatment rates, visual and anatomical outcomes at 1-year postnatal age in infants treated for retinopathy of prematurity (ROP) METHODS: Longitudinal national surveillance study of infants treated for ROP in the United Kingdom between December 2013 and December 2014, supported by the British Ophthalmic Surveillance Unit. Here we report retreatment rates, anatomical, visual and refractive outcomes at 1-year follow-up., Results: One-year follow-up forms were completed for 168 children of the original cohort of 327 (51.4%). Twenty-two had at least one retreatment: 17/153 right eyes (REs, 11.1%) after initial diode laser, and 5/14 REs (35.7%) after initial injection of anti-vascular endothelial growth factor (VEGF) antibody. Median (interquartile range) RE best-corrected visual acuity was 0.6 (0.4-1.0) (n = 46 REs), and median acuity both eyes open 0.4 (0.3-0.7) logMAR (n = 89). Median spherical equivalent (RE) was 0.44 (-1.3 to 1.3) dioptre (D) (n = 116). Median astigmatism (RE) was 0.5 (0-1.0) D (n = 111), and median anisometropia 0.125 (0-0.75) D (n = 116). Twenty-four children (20.5%) had been prescribed glasses. Sight impairment certification eligibility information was available for 131 children: 11 (8.4%) were eligible to be certified as sight impaired, and 5 (3.8%) as severely sight impaired., Conclusions: Retreatment rates are in line with previous reports, and appear higher after initial anti-VEGF antibody than after initial diode laser. Refractive outcomes are in line with previous studies, with a trend towards early emmetropia and myopia following diode laser, particularly in more severe ROP.

In establishing the sources of data variability within sedimentation velocity analysis in the analytical ultracentrifuge and their relative importance, recent studies have demonstrated that alignment of the sample cells to the centre of rotation is the most significant contributing factor to overall variability, particularly for the characterisation of low levels of protein aggregation. Accurate mechanical and optical alignment tools have been recently designed. In this study, we (1) confirm the effect of misalignment observed by others on the estimated amounts of bovine serum albumin (BSA) monomer and dimer, and the sedimentation coefficient value for the BSA dimer; and (2) demonstrate the high performance of a mechanical alignment tool and the usefulness of a simple and complementary enhanced manual alignment protocol which should be useful for situations where these tools are not available.

The heterogeneity and molecular weight of a chitosan of low molecular weight (molar mass) and low degree of acetylation (0.1) for potential use as a consolidant for decayed archaeological wood were examined by sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge before and after depolymerisation. Sedimentation velocity before depolymerisation revealed a uniform distribution of sedimentation coefficient with little concentration dependence. SEDFIT-MSTAR analysis revealed a weight average molecular weight M w of (14.2 ± 1.2) kDa, and polydispersity index of ~ 1.2. Further analysis using MULTISIG revealed a distribution of material between 2 and 20 kDa and consistent with the weight average M w . Controlled depolymerisation using hydrogen peroxide and ultra-violet radiation in an acetic acid medium reduced this to (4.9 ± 0.7) kDa, with a similar polydispersity. The depolymerised material appears to be within the range that has been predicted to fully penetrate into archaeological wood. The consequences for this finding and the use of the analytical ultracentrifuge in wood conservation strategies are considered.

Current saliva testing methods rely on cutting edge yet expensive techniques for the detection and analysis of genetic material, proteins and biomarkers for clinical use. However, these techniques are limited in scope and often cannot be used with complex food materials. We propose an efficient ex-vivo tool for evaluating biologically relevant interactions between food components and human saliva using sedimentation velocity analytical ultracentrifugation (SV-AUC). We evaluated macromolecular content from "unstimulated" (US) and "stimulated" (SS) samples pooled from 5 healthy volunteers. Over 90% of total saliva protein consisted of α-amylase and mucin, and up to 10% was secretory immunoglobulin A (SIgA). It was shown that α-amylase concentration increased upon parafilm stimulation, which lead to a decrease in the viscosity of saliva. Then, we used a simple food system (green tea) to evaluate changes in the salivary protein content caused by green tea polyphenols. It was found that aroma release from green tea is highly influenced by interactions between α-amylase and polyphenol epigallocatechin 3-gallate (EGCG). This interaction was found to increase the viscosity of the salivary bulk, suggested to contribute to astringency, and increased the concentrations of β-ionone, benzaldehyde and isovaleraldehyde (P < 0.01), suggested to play a significant role in the characteristic flavour of green tea.

Beta 1-3, 1-4 glucans ("beta-glucans") are one of the key components of the cell wall of cereals, complementing the main structural component cellulose. Beta-glucans are also an important source of soluble fibre in foods containing oats with claims of other beneficial nutritional properties such as plasma cholesterol lowering in humans. Key to the function of beta-glucans is their molecular weight and because of their high polydispersity - molecular weight distribution. Analytical ultracentrifugation provides a matrix-free approach (not requiring separation columns or media) to polymer molecular weight distribution determination. The sedimentation coefficient distribution is converted to a molecular weight distribution via a power law relation using an established procedure known as the Extended Fujita approach. We establish and apply the power law relation and Extended Fujita method for the first time to a series of native and processed oat beta-glucans. The application of this approach to beta-glucans from other sources is considered.

An increasing number of Australians are being admitted to hospitals and day procedure centers to have dental treatment under a dental general anesthetic (DGA). Children younger than 2 y are having DGAs. These operations are costly and, although there have been improvements in safety, are not without risk. Most DGAs in children are to treat dental caries and have been defined as potentially preventable dental hospitalizations (PPDHs). This article reports on an analysis of the impact of access to community water fluoridation (CWF), availability of oral health professionals (OHPs), and socioeconomic status (SES) on PPDHs of 0- to 4-y-olds in 2012-2013 in Victoria, Australia. Data on these variables were obtained at the community (postcode) level. From the negative binomial multivariate analysis, each of the 3 independent variables was independently significantly associated with PPDHs at the postcode level. Children residing in postcodes without CWF on average had 59% higher rates than those with access (incident rate ratio [IRR], 1.59; P < 0.0001), children in postcodes with the lowest level of availability of OHPs had 65% higher rates than those with the highest access (IRR, 1.65; P < 0.0001), and children living in the most disadvantaged SES quintiles had 57% higher rates than children in the most advantaged quintiles (IRR, 1.57; P < 0.0001). There was a stepwise social gradient by SES quintile. In analysis of access to CWF and SES status, children without access to CWF had 86% higher PPDH rates than children with access (IRR, 1.86; P < 0.0001). In summary, no access to CWF, poor availability of OHPs, and lower SES status were independently associated with higher PPDH rates among 0- to 4-y-olds in Victoria at the postcode level. The study highlights the importance of considering 3 interacting factors-access to CWF, access to OHPs, and SES-in efforts to reduce PPDH rates in young children. Knowledge Transfer Statement: Extending access to water fluoridation, increasing the availability of dental services, and raising disadvantaged families' socioeconomic status are each likely to decrease the rate of dental general anesthetics in young children.

Background: The World Health Organization (WHO) states that diabetic foot ulcers (DFU) are associated with disability, death among patients with diabetes and substantial costs, if not prevented or managed effectively. The aim here is to examine the effectiveness of patient education in preventing and reducing the incidence or recurrence of adult DFU and amputation., Methods: A systematic review and meta-analysis of randomised clinical trials (RCTs) in adults aged 18+ who have diabetes mellitus (type 1 or type 2) or DFU. CINAHL, EMBASE, MEDLINE, PSYCINFO, Cochrane Library and Evidence-Based Nursing, National Library for Health, Medica and Google Scholar were searched. Only English language studies were considered. Databases were searched from their inception to September 2017., Findings: Six RCTs met the inclusion criteria. Only five RCTs reported on the incidence of DFU whilst only two reported on amputation rates. There was no advantage of combining different educational approaches in preventing/reducing DFU, relative risk (RR) of 0.50 (95%CI 0.21, 1.17) (P = 0.11). Two RCTs based on foot care education alone were compared with usual care; the result showed a non-significant effect (P = 0.57) with high heterogeneity of 77%.Analysis based on intensive versus brief educational approach showed a statistically reduced risk of incidence of DFU in the intervention group when compared to the control group; (RR, 0.37, 95%CI 0.14, 1.01) (P = 0.05) with high heterogeneity of 91%., Interpretation: The intensive educational intervention was associated with reduced incidence of DFU.

The structure and function of clinical dosage insulin and its analogues were assessed. This included 'native insulins' (human recombinant, bovine, porcine), 'fast-acting analogues' (aspart, glulisine, lispro) and 'slow-acting analogues' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

Aim: The aim of the present study was to determine the validity of quantitative light-induced fluorescence-digital (QLF-D) in regard to the detection and quantification of developmental demarcated hypomineralized lesions of enamel in vitro when compared to micro-computed tomography (CT) determination of lesion characteristics. A secondary aim was to develop a protocol for 3-D analysis using micro-CT., Methods: Twenty-four hypomineralized defects were classified as cream/white (CW), yellow/brown (YB), and post-eruptive breakdown. Teeth were scanned using micro-CT. Grayscale and chromatic vertical sections were constructed. Mineral density and porosity percentage were calculated. Fluorescence loss and red fluorescence were determined from images. Linear mixed models were computed., Results: Mineral density and porosity mean values by lesion type were statistically different (P<.001). CW lesions had lower fluorescence loss than YB and broken lesions. Red fluorescence was emitted by the majority of the defects, and the means between lesion types were statistically different (P<.001). The mixed model indicated that mineral density was not correlated with fluorescence loss and lesion type., Conclusion: The present findings support QLF-D as a method to detect hypomineralized lesions of different clinical presentation, with red fluorescence putatively related to the severity of the defects. The micro-CT 3-D approach is a reliable method to analyze structural changes in hypomineralized enamel., (© 2017 John Wiley & Sons Australia, Ltd.)

The reversibility and strength of the previously established dimerization of the important glycopeptide antibiotic vancomycin in four different aqueous solvents (including a medically-used formulation) have been studied using short-column sedimentation equilibrium in the analytical ultracentrifuge and model-independent SEDFIT-MSTAR analysis across a range of loading concentrations. The change in the weight average molar mass M w with loading concentration was consistent with a monomer-dimer equilibrium. Overlap of data sets of point weight average molar masses M w (r) versus local concentration c(r) for different loading concentrations demonstrated a completely reversible equilibrium process. At the clinical infusion concentration of 5 mg.mL -1 all glycopeptide is dimerized whilst at 19 µg.mL -1 (a clinical target trough serum concentration), vancomycin was mainly monomeric (<20% dimerized). Analysis of the variation of M w with loading concentration revealed dissociation constants in the range 25-75 μM, commensurate with a relatively weak association. The effect of two-fold vancomycin (19 µg.mL -1 ) appears to have no effect on the monomeric enterococcal VanS kinase involved in glycopeptide resistance regulation. Therefore, the 30% increase in sedimentation coefficient of VanS on adding vancomycin observed previously is more likely to be due to a ligand-induced conformational change of VanS to a more compact form rather than a ligand-induced dimerization.

Introduction: Iatrogenic damage to the tooth surface in the form of enamel tearouts can occur during removal of fixed orthodontic appliances. The aim of this study was to assess debonded metal and ceramic brackets attached with a variety of bonding materials to determine how frequently this type of damage occurs., Methods: Eighty-one patients close to finishing fixed orthodontic treatment were recruited. They had metal brackets bonded with composite resin and a 2-step etch-and-bond technique or ceramic brackets bonded with composite resin and a 2-step etch-and- bond technique, and composite resin with a self-etching primer or resin-modified glass ionomer cement. Debonded brackets were examined by backscattered scanning electron microscopy with energy dispersive x-ray spectroscopy to determine the presence and area of enamel on the base pad., Results: Of the 486 brackets collected, 26.1% exhibited enamel on the bonding material on the bracket base pad. The incidences of enamel tearouts for each group were metal brackets, 13.3%; ceramic brackets, 30.2%; composite resin with self-etching primer, 38.2%; and resin-modified glass ionomer cement, 21.2%. The percentage of the bracket base pad covered in enamel was highly variable, ranging from 0% to 46.1%., Conclusions: Enamel damage regularly occurred during the debonding process with the degree of damage being highly variable. Damage occurred more frequently when ceramic brackets were used (31.9%) compared with metal brackets (13.3%). Removal of ceramic brackets bonded with resin-modified glass ionomer cement resulted in less damage compared with the resin bonding systems., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers ("multi-hexamerisation"). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24-40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes.

Background: Carbohydrate is accepted as the principal nutrient affecting blood glucose in diabetes; however, current guidelines are unable to specify the optimal quantity of carbohydrate for glycaemic control. No studies exist that describe current practice amongst healthcare professionals giving carbohydrate advice in type 2 diabetes. The present study aims to improve understanding of the degree of variation in the current practice of UK registered dietitians (RDs) by describing how RDs advise patients., Methods: UK RDs were contacted through national networks and asked to complete an online survey, which was analysed using stata, version 12 (StataCorp, College Station, TX, USA). Three consultations between dietitians and patients with type 2 diabetes were observed, followed by semi-structured interviews with the dietitians., Results: In total, 320 complete survey responses were received. Dietitians' advice varied according to expertise, training and confidence, and the complexity of the patient's blood glucose treatment. Some 48% (n = 154) of respondents advised patients to restrict carbohydrate intake either occasionally or frequently, with 35.6% (n = 114) considering 30-39% of total energy from carbohydrate to be a realistic expectation. The overall theme from the interviews was 'Conflicting Priorities', with three sub-themes: (i) how treatment decisions are made; (ii) the difference between empowerment and advice; and (iii) contradictory advice. A disparity existed between what was observed and interview data on how dietitians rationalise the type of carbohydrate advice provided., Conclusions: Dietitians' advice varies for a number of reasons. Consensus exists in some areas (e.g. carbohydrate awareness advice); however, clear definitions of such terms are lacking. Clarification of interventions may improve the consistency of approach and improve patient outcomes., (© 2016 The British Dietetic Association Ltd.)

Introduction: Vertical deviations in thyroid eye disease (TED) can present a surgical challenge due to the difficulty and unpredictability of surgery and the high risk of postoperative drift towards overcorrection. This study reports the postoperative outcomes of patients who underwent adjustable vertical strabismus surgery with Vicryl sutures for thyroid eye disease., Methods: We reviewed the records of patients seen for vertical TED strabismus surgery from January 2005 through December 2009. Clinical details were recorded preoperatively, post-adjustment, and at 3 weeks, 3 months, and 1 year postoperatively., Results: The study included 42 patients. Mean age was 62.4 years and 70% were female. All patients were diplopic preoperatively. The mean near vertical deviation was 21.1 prism diopters (PD) preoperatively, 4.0 PD at 3 weeks postoperatively, 5.0 PD at 3 months, and 4.4 PD at 1 year (all mean results representing undercorrection). 71.4% were free of diplopia postoperatively. Seven patients required further surgery, 2 patients needed further botulinum toxin A. Eight patients experienced an overcorrection; five at 3 weeks, seven at 3 months, and eight at 1 year. There was a significant difference in the mean near angle at tie-off post-adjustment in the patients that overcorrected compared to those that did not reverse (3.1 PD vs 7.1 PD; P=0.005)., Discussion: Adjustable surgery for vertical strabismus in thyroid eye disease may result in late overcorrection and the need for further intervention. We propose that aiming for an immediate post-adjustment angle of 8 PD undercorrection for near would allow for postoperative drift and reduce the chances of a late overcorrection. This would require careful preoperative counseling of the patient in order to explain that immediate undercorrection and persistent diplopia were necessary in order to generate a better long-term result.

VanA-type resistance to glycopeptide antibiotics in clinical enterococci is regulated by the VanS A R A two-component signal transduction system. The nature of the molecular ligand that is recognised by the VanS A sensory component has not hitherto been identified. Here we employ purified, intact and active VanS A membrane protein (henceforth referred to as VanS) in analytical ultracentrifugation experiments to study VanS oligomeric state and conformation in the absence and presence of vancomycin. A combination of sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge (SEDFIT, SEDFIT-MSTAR and MULTISIG analysis) showed that VanS in the absence of the ligand is almost entirely monomeric (molar mass M = 45.7 kDa) in dilute aqueous solution with a trace amount of high molar mass material (M ~ 200 kDa). The sedimentation coefficient s suggests the monomer adopts an extended conformation in aqueous solution with an equivalent aspect ratio of ~(12 ± 2). In the presence of vancomycin over a 33% increase in the sedimentation coefficient is observed with the appearance of additional higher s components, demonstrating an interaction, an observation consistent with our circular dichroism measurements. The two possible causes of this increase in s - either a ligand induced dimerization and/or compaction of the monomer are considered.

Polysaccharides, the most abundant biopolymers, are required for a host of activities in lower organisms, animals, and plants. Their solution characterization is challenging due to their complex shape, heterogeneity, and size. Here, recently developed data analysis approaches were applied for traditional sedimentation equilibrium and velocity methods in order to investigate the molar mass distribution(s) of a subtype of polysaccharide, namely, mannans from four Candida spp. The molecular weight distributions of these mannans were studied using two recently developed equilibrium approaches: SEDFIT-MSTAR and MULTISIG, resulting in corroboratory distribution profiles. Additionally, sedimentation velocity data for all four mannans, analyzed using ls-g*(s) and Extended Fujita approaches, suggest that two of the fungal mannans (FM-1 and FM-3) have a unimodal distribution of molecular species whereas two others (FM-2 and FM-4) displayed bi-modal and broad distributions, respectively: this demonstrates considerable molecular heterogeneity in these polysaccharides, consistent with previous observations of mannans and polysaccharides in general. These methods not only have applications for the characterization of mannans but for other biopolymers such as polysaccharides, DNA, and proteins (including intrinsically disordered proteins).