Review of Indigenous Oral Health

Indigenous Australians1 have poorer oral health than other Australians [1, 2]. Indigenous people suffer from more caries, periodontal diseases, and tooth loss than non-Indigenous people [3]. Tooth decay among the Indigenous population more commonly goes untreated, leading to more extractions. This discrepancy is attributed in part to the fact that access to culturally appropriate and timely dental care is often not available to Indigenous people, especially in rural and remote areas. Other information on oral health such as culturally appropriate resources about maintaining healthy teeth and mouths, and nutritional guidance on how much sugar is contained in certain foods and drinks, is also less available for the Indigenous Australian population. If Indigenous oral health is to be ameliorated, access to dental care must be improved, and an integrated holistic approach to oral health, which includes preventative measures, needs to be established

Topical rosiglitazone is an effective anti-scarring agent in the cornea

Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas

Loose packings of frictional spheres

We have produced loose packings of cohesionless, frictional spheres by sequential deposition of highly-spherical, monodisperse particles through a fluid. By varying the properties of the fluid and the particles, we have identified the Stokes number (St) - rather than the buoyancy of the particles in the fluid - as the parameter controlling the approach to the loose packing limit. The loose packing limit is attained at a threshold value of St at which the kinetic energy of a particle impinging on the packing is fully dissipated by the fluid. Thus, for cohesionless particles, the dynamics of the deposition process, rather than the stability of the static packing, defines the random loose packing limit. We have made direct measurements of the interparticle friction in the fluid, and present an experimental measurement of the loose packing volume fraction, \phi_{RLP}, as a function of the friction coefficient \mu_s.Comment: 6 pages, 5 figure

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Evaluating pharmacist input into the pharmaceutical care of patients in dispensing medical practices in remote and rural areas of Scotland.

Background. - The Highlands and the Western Isles are the two most remote and rural areas of Scotland, with many medical practices in areas where pharmacies would not be viable. Recent regulations state that that dispensing medical practices in these areas must receive pharmacist support for patients who would benefit. Objective. - This study aimed to evaluate pilot services, which centred on the provision of patient centred pharmaceutical care. Methods. A realist type evaluation was conducted by an independent research team comprising collecting quantitative data around what occurred during the consultation followed by interviews with purposive samples of staff (n = 14) and patients (n = 18). Results. - A total of 873 medicines related issues were identified in 473 patients reviewed, with the main issue being 'inappropriate dose, frequency, duration'. Just under half (39.7%) of issues were managed by the pharmacist without any medical input. Interviews indicated a high level of appreciation, although there was an increase in workload for some staff. While the need for telephone based pharmacist consultations for some patients was understood, there was a preference for face to face. All were supportive of continuing and extending the service. Conclusion. - The clinical pharmacist service was both needed and valued highly by staff and patients. In Scotland, this aligns with the Government vision and action plan, 'Prescription for Excellence', that by 2023 all patient facing pharmacists will be independent prescribers with those in remote and rural areas entitled to 'equity of access to such expertise'

A Comprehensive GC–MS Sub-Microscale Assay for Fatty Acids and its Applications

Fatty acid analysis is essential to a broad range of applications including those associated with the nascent algal biofuel and algal bioproduct industries. Current fatty acid profiling methods require lengthy, sequential extraction and transesterification steps necessitating significant quantities of analyte. We report the development of a rapid, microscale, single-step, in situ protocol for GC–MS lipid analysis that requires only 250 μg dry mass per sample. We furthermore demonstrate the broad applications of this technique by profiling the fatty acids of several algal species, small aquatic organisms, insects and terrestrial plant material. When combined with fluorescent techniques utilizing the BODIPY dye family and flow cytometry, this micro-assay serves as a powerful tool for analyzing fatty acids in laboratory and field collected samples, for high-throughput screening, and for crop assessment. Additionally, the high sensitivity of the technique allows for population analyses across a wide variety of taxa

Sex-Specific Parental Effects on Offspring Lipid Levels

Background: Plasma lipid levels are highly heritable traits, but known genetic loci can only explain a small portion of their heritability. Methods and Results: In this study, we analyzed the role of parental levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TGs) in explaining the values of the corresponding traits in adult offspring. We also evaluated the contribution of nongenetic factors that influence lipid traits (age, body mass index, smoking, medications, and menopause) alone and in combination with variability at the genetic loci known to associate with TC, LDL‐C, HDL‐C, and TG levels. We performed comparisons among different sex‐specific regression models in 416 families from the Framingham Heart Study and 304 from the SardiNIA cohort. Models including parental lipid levels explain significantly more of the trait variation than models without these measures, explaining up to ≈39% of the total trait variation. Of this variation, the parent‐of‐origin effect explains as much as ≈15% and it does so in a sex‐specific way. This observation is not owing to shared environment, given that spouse‐pair correlations were negligible (\u3c1.5% explained variation in all cases) and is distinct from previous genetic and acquired factors that are known to influence serum lipid levels. Conclusions: These findings support the concept that unknown genetic and epigenetic contributors are responsible for most of the heritable component of the plasma lipid phenotype, and that, at present, the clinical utility of knowing age‐matched parental lipid levels in assessing risk of dyslipidemia supersedes individual locus effects. Our results support the clinical utility of knowing parental lipid levels in assessing future risk of dyslipidemia

Investigating the Potential Role of Genetic and Epigenetic Variation of DNA Methyltransferase Genes in Hyperplastic Polyposis Syndrome

BACKGROUND: Hyperplastic Polyposis Syndrome (HPS) is a condition associated with multiple serrated polyps, and an increased risk of colorectal cancer (CRC). At least half of CRCs arising in HPS show a CpG island methylator phenotype (CIMP), potentially linked to aberrant DNA methyltransferase (DNMT) activity. CIMP is associated with methylation of tumor suppressor genes including regulators of DNA mismatch repair (such as MLH1, MGMT), and negative regulators of Wnt signaling (such as WIF1). In this study, we investigated the potential for interaction of genetic and epigenetic variation in DNMT genes, in the aetiology of HPS. METHODS: We utilized high resolution melting (HRM) analysis to screen 45 cases with HPS for novel sequence variants in DNMT1, DNMT3A, DNMT3B, and DNMT3L. 21 polyps from 13 patients were screened for BRAF and KRAS mutations, with assessment of promoter methylation in the DNMT1, DNMT3A, DNMT3B, DNMT3L MLH1, MGMT, and WIF1 gene promoters. RESULTS: No pathologic germline mutations were observed in any DNA-methyltransferase gene. However, the T allele of rs62106244 (intron 10 of DNMT1 gene) was over-represented in cases with HPS (p<0.01) compared with population controls. The DNMT1, DNMT3A and DNMT3B promoters were unmethylated in all instances. Interestingly, the DNMT3L promoter showed low levels of methylation in polyps and normal colonic mucosa relative to matched disease free cells with methylation level negatively correlated to expression level in normal colonic tissue. DNMT3L promoter hypomethylation was more often found in polyps harbouring KRAS mutations (p = 0.0053). BRAF mutations were common (11 out of 21 polyps), whilst KRAS mutations were identified in 4 of 21 polyps. CONCLUSIONS: Genetic or epigenetic alterations in DNMT genes do not appear to be associated with HPS, but further investigation of genetic variation at rs62106244 is justified given the high frequency of the minor allele in this case series.Musa Drini, Nicholas C. Wong, Hamish S. Scott, Jeffrey M. Craig, Alexander Dobrovic, Chelsee A. Hewitt, Christofer Dow, Joanne P. Young, Mark A. Jenkins, Richard Saffery and Finlay A. Macra