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Changes in mineral density and nanomechanical properties of enamel white spot lesions by dentifrices with different active ingredients for remineralisation - an in vitro study.
No full textObjectives:This study aims to evaluate the remineralisation potential of fluoridated dentifrices with added active ingredients compared to a standard fluoride dentifrice with no additional active ingredients.
Methods: Artificial demineralised enamel lesions were formed by placing premolars into demineralising solution. The teeth were randomly assigned to 4 groups and subjected to 10-days pH cycling: Group 1: Sensodyne repair and protect® containing Novamin®; Group 2: Clinpro Tooth Crème® containing functionalised tricalcium phosphate; Group 3: Colgate® Cavity Protection containing 1450ppm fluoride; Group 4: Distilled water. Mineral density (MD) was assessed using Micro-CT while elastic modulus (EM) and hardness (H) were assessed using nanomechanical testing.
Results: Mean MD percentage gain was highest in Groups 1 and 2, followed by Group 3 and lowest in Group 4. There was no significant difference in mean MD percentage gain between Groups 1 and 2. Also, no significant differences were evident in the EM and H between the outer layer of the treated lesions of Group 1, Group 2 and Group 3 which were significantly higher than Group 4. The EM and H of the inner layer of the treated lesions were highest in Groups 1 and 2, followed by Group 3 and lowest in Group 4.
Conclusions: All tested dentifrices effectively remineralised the demineralised enamel lesions. The added active ingredients penetrated and remineralised the deeper parts of the carious lesions. However, there was no significant difference in remineralisation at the lesion surface between the tested dentifrices.
Clinical Significance: The use of dentifrices with enhanced remineralisation potential would benefit population with high caries risk and those with limited access to dental care. This could lead to a decrease in cavitated carious lesions and a reduction in the burden of treatment costs to patients and funding bodies
What’s in a Smile? An investigation of the effect of ethnic background on smiling features
Get PDFObjectives: The Fijian smile, also called the “Bula Smile,” is often described as the world’s friendliest. The description of Bula Smile, however, remains anecdotal. This project aimed to describe and compare the features of Fijians’ smiles with those of New Zealand Europeans.
Methods:
An observational study was conducted on two ethnic groups, Fijians (FJ; N=23) and New Zealand Europeans (NZ; N=23), matched for age and gender. All participants were asked to watch a series of amusing videos, and their reactions were recorded using a 4K web camera. The videos were analysed using bespoke pattern recognition software to assess the frequency, duration, intensity, and genuineness of smiling episodes. The software had been previously validated against the Facial Action Coding Systems (FACS) Action Units 6 (AU6 - cheek raiser), 12 (AU12 - lip corner puller), and 25 (AU25 – lips apart) (see Chapter 2 for details). The participants also completed a 60-item personality (IPIP NEO) and the Smile Esthetics-Related Quality of Life measures (SERQoL). Malocclusions were assessed using the Dental Aesthetic Index (DAI). Data were analysed by generalised linear models.
Results:
Fijians smiled longer than New Zealand Europeans (+19.9%; p=0.027), but the number of smiles per minute did not differ between groups (p=0.083). Mean intensity of AU6 (+1.0; 95%CIs=0.6-1.5; p<0.001), AU12 (+0.5; 95%CIs=0.1-0.9; p=0.008) and AU25 (+22.3%; 95%CIs=7.3-37.3%; p=0.005) were all significantly higher in FJ group than in NZ group. Compared to the NZ group, the FJ group scored lower on openness (-4.0; P=0.026) and higher on SERQoL (+3.0; P=0.003), the latter indicating less confidence with their smile. The DAI index did not differ between the two ethnic groups.
Conclusion:
Smiling features of Fijians and New Zealanders showed objective differences, as represented by the mean activity of FACS AUs, which could not be explained by personality traits, self-confidence with their smile, and malocclusion severity. The most distinctive trait of the Fijians smile was the higher activation of the Duchenne’s marker (AU6), which indicates “smiling with the eyes”, and is regarded as a sign of smile genuineness
Vancomycin AUC optimisation using minimal plasma concentration monitoring
Get PDFVancomycin is an antibiotic administered intravenously for severe invasive infections and due to its low therapeutic index, therapeutic drug monitoring is recommended. Clinical staff at the Canterbury District Health Board (CDHB) have been monitoring serum concentrations and targeting a Cmin of 15-20 mg/L. The 2020 guidelines from the Infectious Diseases Society of America (IDSA) recommend directly monitoring the AUC0-24h/MICBMD for Methicillin Resistant Staphylococcus Aureus due to: increased rates of target attainment, reduced overexposure and that this metric accounts for bacterial susceptibility compared to Cmin values. The value of AUC24 can be difficult to estimate, requiring several concentrations across a dose profile, using empirical estimates or specialised software. Clinical staff at the CDHB have access to a Bayesian forecasting software, TCIWorks with the Thomson et al. model implemented; to date there has been no evaluation of the accuracy of a limited sampling strategy combined with this solution.
This research had three aims: 1) To determine whether a limited vancomycin sampling strategy (1-2 samples per dosing interval, using Bayesian methods) can accurately predict the AUC0-24h at steady state (AUCss0-24h) of vancomycin in adults, 2) to determine whether accuracy in the AUCss0-24h predictions differs between obese and non-obese patients, and, 3) to investigate factors contributing to bias in the AUCss0-24h estimate. A simulation study was undertaken using demographic dosing data from patients administered vancomycin at the CDHB between 2016 and 2019 and nine sampling strategies where 1-2 simulated samples were included in the Bayesian forecasting per course, varying the day of the sample(s). Values of mean prediction error (mg.h/L) and AUC of the sample strategy versus a simulated reference AUC (AUCssTest: 0-24h/AUCssRef: 0-24h) were calculated for each sample strategy and the latter was compared to a bioequivalence range recommended for low therapeutic index medications (0.900-1.111). To estimate the accuracy of each sampling strategy, the proportion of values of AUCssTest: 0-24h within 20% of the AUCssRef: -24h was calculated (P20).
It was found that the sampling strategies were unable to estimate an unbiased result across the dataset; all strategies significantly underestimated the value of AUCssTest: 0-24h (mean prediction error: -70.52 (95% CI -97.37, -43.68) to -59.08 (95% CI -77.13, -41.02)) and only one strategy met the bioequivalence criteria; using the Cmin for doses 2 and 3. Stratification by obesity status found bias in obese individuals but not non-obese individuals. This was corroborated by the multilinear regression model which found that BMI was a significant predictor of the prediction error (coefficient -4.50 (95% CI -7.06, -1.94); p < 0.001).
This research provided useful information that any of the strategies implemented could estimate AUCss0-24h in non-obese individuals with sufficient accuracy. Further research into strategies for obese individuals is required
Characterising spontaneous revertants in the cyanobacterium Synechocystis sp. PCC 6803
No full textThe cyanobacterium Synechocystis sp. PCC 6803 (hereafter Synechocystis 6803) is a model organism used extensively to study photosynthesis and environmental stress responses. Its ability to integrate foreign DNA into its genome makes it a valuable organism for genetic engineering. Similar to many other cyanobacterial species, Synechocystis 6803 is able to grow photoautotrophically at neutral to alkaline pH ranges. Interestingly, strains carrying mutations in the PS II extrinsic proteins display a pH-sensitive phenotype where strains grow photoautotropically at pH 10.0 but growth is inhibited at pH 7.5. This project focuses on the pH-sensitive mutant ΔPsbV:ΔCyanoQ. Constant exposure of the ΔPsbV:ΔCyanoQ mutant to pH 7.5 has resulted in a response that restored photoautotrophic growth of two ΔPsbV:ΔCyanoQ mutant cultures. These pseudorevertant strains have switched from the mutated trait to the original phenotype. The two pseudorevertants were isolated: ΔPsbV:ΔCyanoQrev1 and ΔPsbV:ΔCyanoQrev2. Characterisation of the two pseudorevertants, revealed that the ΔPsbV:ΔCyanoQrev1 pseudorevertant, is able to assemble PS II and evolve oxygen. The ΔPsbV:ΔCyanoQrev2 pseudorevertant, can also assemble PS II, evolve oxygen and transfer electrons from PS II to QA and QB. To gain an understanding of what has occurred within the two pseudorevertant strains to allow growth in BG-11 buffered at pH 7.5, whole genome sequencing was conducted to isolate candidate genes that could be responsible for growth. Although, there were no candidate genes obtained for the ΔPsbV:ΔCyanoQrev1 pseudorevertant, other possible factors were considered such as the expression of known stress-response genes and sigma factors that could contribute to the growth of the ΔPsbV:ΔCyanoQrev1. In contrast, the candidate genes that were isolated from the ΔPsbV:ΔCyanoQrev2 pseudorevertant are thioredoxin C (trxC) and Photosystem II (PS II) manganese stabilizing protein (psbO). The trxC gene does not have a well-established function in Synechocystis 6803; however, thioredoxins are important for the regulation of proteins and enzymatic pathways. On the other hand, the psbO gene stabilizes the manganese cluster for oxygen evolution. This study indicates that both the trxC and psbO are two potential genes that could be involved in growth restoration of pH-sensitive strains in pH 7.5
Spaces of phylogenetic time trees
Get PDFTime trees are evolutionary histories (also called phylogenies) that include times of evolutionary events. They arise in many applications, including cancer and virus evolution. Of particular interest are clock-like trees, where all leaves have equal distance to the root. These can be randomly sampled using the coalescent model, and a number of software packages for reconstructing trees from sequence data do so.
Most such inference methods use tree search algorithms, which require a tree space over which the inference is performed. These typically output a distribution of trees, which needs to be interpreted. Currently, most methods use consensus trees to summarise the output. Statistical methods such as mean trees and confidence regions would be preferable, however such methods are largely undeveloped for tree spaces.
It is essential for the development of such methods to explore the geometry
of tree spaces. Most tree spaces are based on tree rearrangement operations, which apply local changes to a tree to propose trees that are similar to a given tree. Popular tree rearrangements are Nearest Neighbour Interchange, Subtree Prune and Regraft, and Tree Bisection and Reconnection. For all three tree rearrangements, the problem of computing distances, which are defined as the minimum number of tree rearrangements needed to transform one tree into the other, is NP-hard, making tree inference and comparison
algorithms challenging to design in practice.
In this thesis, we introduce discrete coalescent trees, a discretisation of time trees that is motivated by the coalescent model. We then define tree rearrangement operations on discrete coalescent trees, which leads to a new tree space DCTm. We analyse this tree space, focussing on properties that are essential to establish statistical measures such as mean trees and confidence regions. Our results include a polynomial-time algorithm for computing shortest paths in DCTm, making this the first tree rearrangement based tree space in which distances can be computed efficiently. We also analyse geometrical properties of our tree space DCTm, and shortest paths within the space. As a special case of discrete coalescent trees we consider ranked trees. We also discuss unlabelled time trees and two different tree spaces that result from considering tree rearrangement operations on them, one of which can be interpreted as the unlabelled version of DCTm
Randomised controlled pilot trial comparing low dose and very low- dose microdrop administration of phenylephrine and cyclopentolate for retinopathy of prematurity eye examinations in neonates
Get PDFAims To determine if
Very low dose mydriatic eye microdrop regimen sufficiently dilates the pupil (above 4.1 mm) compared with the currently used low dose mydriatic eye microdrop regimen.
Cardiovascular, gastrointestinal and respiratory adverse effects occur following eye drop instillation.
Methods Seventeen premature infants were recruited into this prospective, randomised controlled pilot trial in January 2017 to November 2018. Data were collected from the single-centre Neonatal Intensive Care Unit, Dunedin Hospital, New Zealand. The inclusion criteria were birth weight less than 1500 g or gestational age less than 31 weeks, or any premature infant requiring red reflex testing. Infants were randomised to receive either phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1%, 1 microdrop in both eyes. Efficacy outcome measures were pupil size at retinopathy of prematurity eye examination (ROPEE) and ophthalmologist rating of ease of screen.
Results All participants had sufficient pupillary dilation for a successful ROPEE. Ophthalmologists rated the ROPEE as easy for 90% of all examinations. Pupil dilation measurements at the time of examination, mean±SD, 4.8±0.2 (95% CI 4.5 to 5.2) mm for treatment A and 5±0.2 (95%CI 4.6 to 5.4) mm for treatment B (p=0.61). There were no statistically significant differences between the groups for safety data.
Conclusions Very low dose microdrop administration of phenylephrine and cyclopentolate appears to be effective at sufficiently dilating the neonatal pupil for ROPEEs. Low dose and very low dose microdrop mydriatic regimens may also reduce the risk of unwanted adverse effects associated with these medicines.Peer Reviewe
The unique effects of individual folate vitamers on cancer incidence and outcomes: a protocol for a systematic review and meta-analysis.
No full textThe importance of folic acid supplementation in reducing the risk of neural tube defects is well established. However, the effects of folic acid on other diseases, including cancer, are less well understood and have been the subject of several clinical trials. Folate vitamers are chemically similar substances derived from the parent compound pteroyl monoglutamic acid. Several placebo-controlled clinical trials have assessed the impact of folate vitamer supplements on cancer incidence and mortality with differing results. Meta-analyses have found an association between folate supplements and cancer outcomes with different estimates of certainty. However, we believe that differentiating between the different vitamer forms will account for much of the heterogeneity seen in the data. This protocol aims to define the methods for a systematic review and meta-analysis to assess if individual folate vitamers modify the risk of cancer incidence and cancer-associated mortality
NZDep2018 analysis of census 2018 variables - DHB05: Waikato
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
U-RHYTHM microdialysis: Towards ambulatory metabolodynamics
Get PDFRhythms characterise the physiology of all living things, and rhythmic patterns can be observed in almost all aspects of daily human life. Disruption of rhythms is linked to poor health and may be caused by disease, or desynchrony between activity, behaviour, and internal time cues. Since rhythms are individual and dynamic, single time point assessment provides limited information and is potentially misleading. On the other hand, capturing dynamic information is traditionally difficult and invasive. In this thesis I investigated how these difficulties could be overcome using a novel, prototype portable microdialysis sampling device, U-RHYTHM.
I have shown that U-RHYTHM is a safe, reliable method and well-tolerated by participants. In a series of small proof-of-principle studies using healthy volunteers, the U-RHYTHM device and abdominal subcutaneous microdialysis, diurnal and ultradian rhythms of 8 adrenal steroids were shown and validated against plasma, 7 of which have never previously been described in tissue. Next, using a targeted metabolomics approach, multiple tissue metabolites were found, showing daily- and food-driven rhythms. Finally, in ambulatory studies, the novel detection of tissue melatonin rhythms simultaneously with cortisol and cortisone was achieved and presented alongside rhythmic data from other non-invasive wearable devices. Across all studies, limitations on the technique related to the recovery of some lipophilic, hydrophobic compounds.
These studies show that U-RHYTHM can be used to investigate daily trends, ultradian details, and interactions between rhythmic processes. Data from U-RHYTHM studies could lead to new methods for diagnosis of endocrine and metabolic conditions, and to the increased understanding how lifestyle-related rhythm disruption leads to poor health outcomes. The unintrusive nature of the technique provides the flexibility to investigate in both free living and controlled conditions. Further work is needed to validate findings in a larger population
NZDep2018 analysis of census 2018 variables - TA18: Otorohanga District
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/