Some applications of genetics in dentistry

Genetics is fundamental to an understanding of differences between individuals and between populations. Common minor differences are found within what is generally accepted as the normal range of variation, while relatively unusual but more major differences may be appropriately considered under the heading of pathology. Both major and minor differences occur in terms of structure, function or susceptibility to disease. This submission contains examples of such differences and their exploitation or analysis, most of which fall within the general field of dentistry.A number of observations of inherited dental abnormalities in man and experimental animals are included. These indicate that there can be compensatory interaction between neighbouring tooth germs during development. Based on this interaction, a model to account for differential evolutionary reduction of tooth size is proposed. Studies of regional differentiation in the mouse vertebral column are described, the vertebral column being a series of homologous structures divided into morphological classes in the same way as heterodont dentitions. The effects of a number of inherited disorders of the axial skeleton indicate that vertebral class boundaries in the mouse are established at a very early stage, even before somite formation. The use of dental morphology for population discrimination is discussed in relation to studies of the genetics of dental morphological variation, and a population comparison in which the discriminating power of dental morphology was tested against that provided by known genetic variants.Studies of inherited iron-deficiency anaemia in the mouse are described. They show that the disorder is associated with thinner lingual epithelium than normal and possibly with increased susceptibility to oral candidosis. Different strains of Candida produced different levels of oral colonisation and infection in normal mice, suggesting that susceptibility to candidosis may be related to variation in the microorganism as well as the host. A human family study of Paget's disease of bone is reported. The results are consistent with the hypothesis that Paget's disease is caused by a common virus, with genetic variation for susceptibility to the disease. Also in man, a comparison between carriers of X-linked hypohidrotic ectodermal dysplasia (in whom manifestations of the disease may be limited to minimal hypodontia) and females with hypodontia for other reasons indicates that carriers may be distinguished from among female hypodontia cases in general by means of a reduced sweat pore count.In the past, various genetic principles have been misapplied in dentistry. Two critiques of such misapplications are included, together with contributions to a review of current dental research, undergraduate and postgraduate dental texts, and a major new medical genetics text

The effect of population variation on the accuracy of sex estimates derived from basal occipital discriminant functions

Multiple discriminant functions that estimate sex from the dimensions of the basal occipital have been published. However, as there is limited exploration of basal dimension variation between groups, the accuracy of these functions when applied to archaeological material is unknown. This study compares basal dimensions between four known sex-at-death post-medieval European samples and explores how metric differences impact on the accuracy of sex assessment discriminant functions. Published data from St Bride’s, London (n = 146) and the Georges Olivier collection, Paris (n = 68) were compared with new data from the eighteenth to nineteenth century Dutch Middenbeemster sample (n = 74) and the early twentieth century Rainer sample, Romania (n = 282) using independent t tests. The Middenbeemster and Rainer data were substituted into six published discriminant functions derived from the St Bride’s and the Georges Olivier samples, and the results were compared to their known sex. Multiple statistically significant differences were found between the four groups. Of the six discriminant functions tested, five failed to reach the published accuracy and fell below chance. In addition, even where the samples were statistically comparable in means, trends for difference also impacted the accuracy of discriminant functions. Enough variation in basal occipital dimensions existed in the European groups to decrease the accuracy of sex estimation discriminant functions to unusable. Possible inter-observer error, varying genetic, socioeconomic, and geographical factors are likely causes of dimension variation. This research further highlights the dangers of using sex estimation discriminant functions on samples that differ to the original derivative population and demonstrates the need for more rigorous testing

The stigmatisation of people with chronic back pain

This study responded to the need for better theoretical understanding of experiences that shape the beliefs, attitudes and needs of chronic back patients attending pain clinics. The aim was explore and conceptualise the experiences of people of working age who seek help from pain clinics for chronic back pain. Methods. This was a qualitative study, based on an interpretative phenomenological approach (IPA). During in-depth interviews in their homes, participants were invited to 'tell their story' from the time their pain began. Participants were twelve male and six female patients, aged between 28 and 62 years, diagnosed as having chronic benign back pain. All had recently attended one of two pain clinics as new referrals. The interview transcripts were analysed thematically. Findings. Stigmatisation emerged as a key theme from the narrative accounts of participants. The findings expose subtle as well as overt stigmatising responses by family, friends, health professionals and the general public which appeared to have a profound effect on the perceptions, self esteem and behaviours of those interviewed. Conclusions. The findings suggest that patients with chronic back pain feel stigmatised by the time they attend pain clinics and this may affect their attitudes and behaviours towards those offering professional help. Theories of chronic pain need to accommodate these responses, while pain management programmes need to address the realities and practicalities of dealing with stigma in everyday life

Distinct Impacts of Eda and Edar Loss of Function on the Mouse Dentition

The Eda-A1-Edar signaling pathway is involved in the development of organs with an ectodermal origin, including teeth. In mouse, mutants are known for both the ligand, Eda-A1 (Tabby), and the receptor, Edar (Downless). The adult dentitions of these two mutants have classically been considered to be similar. However, previous studies mentioned differences in embryonic dental development between EdaTa and Edardl-J mutants. A detailed study of tooth morphology in mutants bearing losses of functions of these two genes thus appears necessary to test the pattern variability induced by the developmental modifications. 3D-reconstructions of the cheek teeth have been performed at the ESRF (Grenoble, France) by X-ray synchrotron microtomography to assess dental morphology. The morphological variability observed in EdaTa and Edardl-J mutants have then been compared in detail. Despite patchy similarities, our detailed work on cheek teeth in EdaTa and Edardl-J mice show that all dental morphotypes defined in Edardl-J mice resolutely differ from those of EdaTa mice. This study reveals that losses of function of Eda and Edar have distinct impacts on the tooth size and morphology, contrary to what has previously been thought. The results indicate that unknown mechanisms of the Eda pathway are implicated in tooth morphogenesis. Three hypotheses could explain our results; an unexpected role of the Xedar pathway (which is influenced by the Eda gene product but not that of Edar), a more complex connection than has been appreciated between Edar and another protein, or a ligand-independent activity for Edar. Further work is necessary to test these hypotheses and improve our understanding of the mechanisms of development

"I try and smile, I try and be cheery, I try not to be pushy. I try to say ‘I’m here for help’ but I leave feeling… worried’’: A qualitative study of perceptions of interactions with health professionals by community-based older adults with chronic pain

Background: Over 50% of community-dwelling older adults experience chronic pain, which threatens their quality of life. Of importance to their pain management is older people’s interaction with health professionals that, if unsatisfactory, may impair the outcome. Aims: To add to the limited research specific to older people living with chronic pain in the community, we explored how they perceive their experiences of interacting with health professionals, seeking factors that might optimise these interactions. Methods: Purposive sampling was used to recruit men and women .65 years with self-reported musculoskeletal chronic pain. Qualitative individual interviews and one group interview were undertaken with 23 participants. Data were transcribed verbatim and underwent Framework Analysis. Results: Three themes were identified. Seeking help illustrates issues around why older people in the community may or may not seek help for chronic pain, and highlights the potential involvement of social comparison. Importance of diagnosis illustrates the desire for professional validation of their condition and an aversion to vague explanations based on the person’s age. Being listened to and being heard illustrates the importance of empathic communication and understanding expectations, with due respect for the person’s age. Conclusions: In common with people of all ages, an effective partnership between an older person in pain and health professionals is essential if pain is to be reported, appropriately assessed and managed, because of the subjective nature of pain and its treatment responses. For older people with pain, perception about their age, by both parties in the partnership, is an additional factor that can unnecessarily interfere with the effectiveness of this partnership. Health professionals should engage with older adults to clarify their expectations about pain and its management, which may be influenced by perceptions about age; and to encourage expression of their concerns, which may also be affected by perceptions about age

Medical student teaching in the UK: how well are newly qualified doctors prepared for their role caring for patients with cancer in hospital?

A number of studies have identified problems with undergraduate oncology teaching. We have investigated how well prepared newly qualified doctors (first foundation year, or FY1 doctors) are for treating patients with cancer. Twenty-five FY1 doctors and 15 senior doctors participated in interviews. We turned the emergent themes into a questionnaire for all 5143 UK FY1 doctors in 2005. The response rate was 43% (2062 responses). Sixty-one percent of FY1 doctors had received oncology teaching at medical school, but 31% recalled seeing fewer than 10 patients with cancer. Forty percent of FY1 doctors felt prepared for looking after patients with cancer. Sixty-five percent felt prepared for diagnosing cancer, 15% felt they knew enough about chemotherapy and radiotherapy, and 11% felt prepared for dealing with oncological emergencies. Respondents believed medical students should learn about symptom control (71%) and communication skills (41%). Respondents who had received oncology teaching were more likely to feel prepared for looking after patients with cancer (OR 1.52; 95% CI 1.14–2.04). Preparedness also correlated with exposure to patients with cancer (OR 1.48; 95% CI 1.22–1.79). We have found worryingly low levels of exposure of medical students to patients with cancer. First foundation year doctors lack knowledge about cancer care and symptom control. Oncologists should maintain involvement in undergraduate teaching, and encourage greater involvement of patients in this teaching

General practitioners' perceptions on home medicines reviews: A qualitative analysis

Background: Home Medicines Review (HMR) is an Australian initiative introduced in 2001 to improve quality use of medicines. Medication management services such as HMRs have the potential to reduce medication related problems. In 2011, changes to the HMR program were introduced to allow for referrals directly to accredited pharmacists in addition to the community pharmacy referral model. These changes were introduced to improve efficiency of the process. This study explored the perceptions of Western Australian general practitioners (GPs) on benefits and barriers of the HMR service and process, including their insights into the direct referral model. Methods: Purposive sampling of GPs who had experience ensured that participants had a working knowledge of the HMR service. Semi structured interviews with 24 GPs from 14 metropolitan Western Australian medical centres between March and May 2013. Transcribing and thematic analysis of data were performed. Results: Most GPs had positive attitudes towards the HMR service. Main perceived benefits of the service were poly-pharmacy reduction and education for both the GP and patient. Strategies identified to improve the service were introduction of a standard HMR report template for pharmacists and better use of technology. Whilst reliability and GPs' familiarity were the main perceived benefits of the direct referral model, a number of GPs agreed that patient unfamiliarity with the HMR pharmacist was a barrier. Conclusions: Despite recognition of the value of the HMR service participating GPs were of the opinion that there are aspects of the HMR service that could be improved. As one of the success factors of HMRs is relying on GPs to utilise this service, this study provides valuable insight into issues that need to be addressed to improve HMR uptake

Estimating the Total Number of Susceptibility Variants Underlying Complex Diseases from Genome-Wide Association Studies

Recently genome-wide association studies (GWAS) have identified numerous susceptibility variants for complex diseases. In this study we proposed several approaches to estimate the total number of variants underlying these diseases. We assume that the variance explained by genetic markers (Vg) follow an exponential distribution, which is justified by previous studies on theories of adaptation. Our aim is to fit the observed distribution of Vg from GWAS to its theoretical distribution. The number of variants is obtained by the heritability divided by the estimated mean of the exponential distribution. In practice, due to limited sample sizes, there is insufficient power to detect variants with small effects. Therefore the power was taken into account in fitting. Besides considering the most significant variants, we also tried to relax the significance threshold, allowing more markers to be fitted. The effects of false positive variants were removed by considering the local false discovery rates. In addition, we developed an alternative approach by directly fitting the z-statistics from GWAS to its theoretical distribution. In all cases, the “winner's curse” effect was corrected analytically. Confidence intervals were also derived. Simulations were performed to compare and verify the performance of different estimators (which incorporates various means of winner's curse correction) and the coverage of the proposed analytic confidence intervals. Our methodology only requires summary statistics and is able to handle both binary and continuous traits. Finally we applied the methods to a few real disease examples (lipid traits, type 2 diabetes and Crohn's disease) and estimated that hundreds to nearly a thousand variants underlie these traits

How Can Home Care Patients and Their Caregivers Better Manage Fall Risks by Leveraging Information Technology?

Objectives: From the perspectives of home care patients and caregivers, this study aimed to (a) identify the challenges for better fall-risk management during home care episodes and (b) explore the opportunities for them to leverage health information technology (IT) solutions to improve fall-risk management during home care episodes. Methods: Twelve in-depth semistructured interviews with the patients and caregivers were conducted within a descriptive single case study design in 1 home health agency (HHA) in the mid-Atlantic region of the United States. Results: Patients and caregivers faced challenges to manage fall risks such as unmanaged expectations, deteriorating cognitive abilities, and poor care coordination between the HHA and physician practices. Opportunities to leverage health IT solutions included patient portals, telehealth, and medication reminder apps on smartphones. Conclusion: Effectively leveraging health IT could further empower patients and caregivers to reduce fall risks by acquiring the necessary information and following clinical advice and recommendations. The HHAs could improve the quality of care by adopting IT solutions that show more promise of improving the experiences of patients and caregivers in fall-risk management