Physical and Molecular Processes Controlling the Formation, Structure and Breakdown of the Salivary Pellicle

Objectives: Despite the importance of the pellicle in oral physiological and pathological processes, an understanding of the fundamental physical and molecular mechanisms underlying the structural formation and breakdown of this protein film remains unresolved. Therefore the work carried out herein attempts to elucidate the structural changes that the pellicle undergoes upon exposure to intrinsic and extrinsic factors. Such as; the role that mucins play in pellicle formation, the effect of a changing acidic environment or the structural changes that occur upon contact with dentifrice components. Methods: in vitro adsorbed pellicles were formed from the saliva (stimulated parotid saliva and stimulated whole mouth saliva) of 14 healthy volunteers, and studied using techniques including a quartz crystal microbalance with dissipation monitoring and a dual polarisation interferometer. The pellicles were then exposed to certain food and oral hygiene ingredients to observe the physical (e.g. surface mass, density, thickness and viscoelasticity) and chemical (e.g. protein composition) modifications that the pellicle undergoes when challenged in this way. Results: Mucins present in whole mouth saliva were shown to help form a more viscous pellicle compared to a pellicle formed from mucin free saliva (parotid saliva). Whereas, the pellicle formed from saliva containing 10 mM CaCl2 was more diffuse and less stable compared to pellicles formed from saliva containing 1mM CaCl2. Structural changes in the pellicle also took place upon exposure to pH4 and pH3 3 citrate buffers, changes that may be related to the isoelectric points of the proteins present in the pellicle. Finally, the polyanionic STP molecule was shown to be more effective than SDS at displacing pellicle form hydroxyapatite. Conclusion: This research demonstrated that the composition of saliva has an important effect on the physical properties of the adsorbed pellicle; and lays the foundations as to how regulating the calcium concentration of saliva provides a mechanism that can control the physical properties of the in-vitro formed pellicle. In addition, the structural changes that the pellicle undergoes under differing acidic environments, and upon exposure to components of oral hygiene products, were observed to help understand the mechanisms underlying the formation and breakdown of the salivary pellicle

Program: Featured Lecture, C.S. Lewis: A Plaster Saint.

Program for the Fifteenth Annual William M. Green Distinguished Christian Lecture Program with featured lecturer Dr. Anthony Lee Ash, Professor of Biblical Studies, Abilene Christian University

What is the Impact of the Analysis Method Used for Health State Utility Values on QALYs in Oncology? A Simulation Study Comparing Progression-Based and Time-to-Death Approaches

Background: Health state utility values (‘utilities’) are an integral part of health technology assessment. Though traditionally categorised by disease status in oncology (i.e. progression), several recent assessments have adopted values calculated according to the time that measures were recorded before death. We conducted a simulation study to understand the limitations of each approach, with a focus on mismatches between the way utilities are generated, and analysed. Methods: Survival times were simulated based on published literature, with permutations of three utility generation mechanisms (UGMs) and utility analysis methods (UAMs): (1) progression based, (2) time-to-death based, and (3) a ‘combination approach’. For each analysis quality-adjusted life-years (QALYs) were estimated. Goodness of fit was assessed via percentage mean error (%ME) and mean absolute error (%MAE). Scenario analyses were performed varying individual parameters, with complex scenarios mimicking published studies. The statistical code is provided for transparency and to aid future work in the area. Results: %ME and %MAE were lowest when the correct analysis form was specified (i.e. UGM and UAM aligned). Underestimates were produced when a time-to-death element was present in the UGM but not included in the UAM, while the ‘combined’ UAM produced overestimates irrespective of the UGM. Scenario analysis demonstrated the importance of the volume of available data beyond the initial time period, for example follow-up. Conclusions: We show that the use of an incorrectly or over-specified UAM can result in substantial bias in the estimation of utilities. We present a flowchart to highlight the issues that may be faced

Brain involvement in Duchenne muscular dystrophy: a role for dystrophin isoform Dp71 in cell migration and proliferation

Intelligence of individuals with Duchenne muscular dystrophy (DMD) is lower than the general population. Cognitive impairment, epilepsy, autism and attention deficit hyperactivity disorder are prevalent. Mounting evidence links these symptoms to the loss of dystrophin in the brain; yet central nervous system involvement in DMD has been largely ignored. The most predominant dystrophin isoform in the brain is the smaller Dp71 isoform expressed in neurons and glia. Distal DMD mutations affecting Dp71 expression are linked to cognitive impairment. The function(s) of Dp71 and how its absence can lead to cognitive and behavioural symptoms are not well understood. We are modelling the loss of Dp71 both endogenously in DMD patient-derived fibroblasts (which, in controls, naturally express Dp71) and with siRNA in neuronal and glial cell lines. Four patient fibroblast cell lines, each harbouring a different DMD gene mutation that naturally results in the loss of Dp71 are being studied. Accompanying clinical data confirms these patients display cognitive and/or behavioural symptoms, which is severe for two individuals. Our preliminary findings highlight a role for Dp71 in cell migration and proliferation; alterations in these processes are associated with psychiatric disorders prevalent in DMD such as autism. We will present would healing and proliferation assay data exploring these role(s) and discuss potential molecular mechanisms behind the cognitive and behavioural symptoms observed in DMD. The high risk of neuropsychiatric syndromes in Duchene warrants early intervention to achieve the best possible quality of life; our findings have significant potential to inform ongoing drug development in this area

Mindfulness reduces information avoidance

Mindfulness meditation has been found to influence various important outcomes such as health, stress, depression, productivity, and altruism. We report evidence from a randomised controlled trial on a previously untested effect of mindfulness: information avoidance. We find that a relatively short mindfulness treatment (two weeks, 15 minutes a day) is able to induce a statistically significant reduction in information avoidance – that is, avoiding in formation that may cause worry or regret. Supplementary evidence supports mindfulness’s effects on emotion regulation as a possible mechanism for the effect

Encapsulation of flutriafol fungicide into electrospun biodegredable poly (L-lactide) nanofibers

The application of biodegradable, electrospun nanofibers in agriculture has attracted a lot of interest as they are cost-effective and offer a versatile technique to fabricate eco-friendly, high surface-to-volume ratio and porous nanofibrous structures from polymeric solutions. Flutriafol is a commonly used fungicide in plant protection in Australia. This study aimed to encapsulate flutriafol into poly(L-lactide) (PLLA) nanofibers matrix by optimizing electrospinnig conditions. The PLLA solution was prepared at concentration of PLLA (5% w/w) in chloroform-Aceton (75–25 v/v) containing 10% (w/w) flutriafol relative to the PLLA. The PLLA/flutriafol mixture was fed with a syringe to a basic electrospinning setup. Optimum electrospinning conditions were observed at 32 °C with a flow rate speed of 1mL/ h, and 12kV high voltage. SEM images were used to characterize the morphology of electrospun nanofibers. Energy-dispersive detector (EDS) was employed to identify successful encapsultion of flutrifol into PLLA nanofibers

Mindfulness reduces information avoidance

Mindfulness meditation has been found to influence various important outcomes such as health, stress, depression, productivity, and altruism. We report evidence from a randomised-controlled trial on a previously untested effect of mindfulness: information avoidance. We find that a relatively short mindfulness treatment (two weeks, 15 min a day) is able to induce a reduction in information avoidance — that is, avoiding information that may cause worry or regret. Supplementary evidence supports mindfulness’s effects on emotion regulation as a possible mechanism for the effect

Kinetics of slow release of nitrogen fertiliser from multi-layered nanofibrous structures

Fertilisers are essential in modern agriculture to enhance plant growth, crop production and product quality. Recent research has focused on the development of delivery systems designed to prolong fertiliser release. This study introduces a new technology to encapsulate and release molecules of fertilisers by using multi-layered electrospun nanofibre as a carrier. Single-layer poly L-lactic acid (PLLA) nanofibres loaded with urea were fabricated using electrospinning. Triple-layer nanofibrous structures were produced by electrospinning polyhydroxybutyrate (PHB) nanofibres as external layers with PLLA nanofibres impregnated with urea fertiliser as the middle layer. Scanning electron microscopy (SEM) and Fourier transform infrared spectrophotometry (FTIR) were employed to characterize the morphology of electrospun nanofibres. Urea release dynamic was analysed using a total nitrogen instrument (TNM-1). The results indicated that triple-layered urea-impregnated nanofibrous structures led to lower initial rate of nitrogen release and slower release rate of cumulative nitrogen which extended for more than three months. It is concluded that triple-layer nanofibrous structures have the potential for slow release delivery of fertilisers

Ethnicity and the Writing of Medieval Scottish history

Historians have long tended to define medieval Scottish society in terms of interactions between ethnic groups. This approach was developed over the course of the long nineteenth century, a formative period for the study of medieval Scotland. At that time, many scholars based their analysis upon scientific principles, long since debunked, which held that medieval 'peoples' could only be understood in terms of 'full ethnic packages'. This approach was combined with a positivist historical narrative that defined Germanic Anglo-Saxons and Normans as the harbingers of advances of Civilisation. While the prejudices of that era have largely faded away, the modern discipline still relies all too often on a dualistic ethnic framework. This is particularly evident in a structure of periodisation that draws a clear line between the 'Celtic' eleventh century and the 'Norman' twelfth. Furthermore, dualistic oppositions based on ethnicity continue, particularly in discussions of the law, kingship, lordship and religion

Voretigene Neparvovec for Treating Inherited Retinal Dystrophies Caused by RPE65 Gene Mutations: An Evidence Review Group Perspective of a NICE Highly Specialised Technology Appraisal

The UK National Institute for Health and Care Excellence (NICE) considered evidence for voretigene neparvovec (VN; Luxturna®) for the treatment of RPE65-mediated inherited retinal dystrophies (IRD) within its highly specialised technology programme. This paper summarises the evidence provided by the company; the appraisal of the evidence by the Peninsula Technology Appraisal Group, who were commissioned to act as the independent evidence review group (ERG); and the development of the NICE guidance by the appraisal committee. The evidence presented by the company highlighted the significant lifelong burden of IRD for patients and carers. Evidence to support the effectiveness of VN was lacking, but the available evidence showed a modest, sustained improvement across a variety of vision-related outcomes. While patients would remain visually impaired, the committee considered that VN would prevent further deterioration in vision. The modelling approach used by the company had a number of limitations and relied heavily upon a large volume of clinical expert input to produce cost-effectiveness estimates with large uncertainty around long-term effectiveness. The ERG’s main concerns revolved around these long-term outcomes and the plausibility of utility values. The NICE committee were convinced that the clinical benefits of VN were important and an appropriate use of national health service resources within a specialised service. The committee concluded that a high unmet need existed in patients with RPE65-mediated IRD and that VN represents a step change in the management of this condition