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Approximately 40 years ago periodontists began systematically developing the evidence to treat predictably and prevent gingivitis and periodontitis. More recently, periodontists have been among a small group of skilled dental-implant surgeons leading that revolution in dentistry. Today, much of the mild/localized moderate periodontitis is not treated by periodontists, and an increasing number of implants are placed by dentists with limited surgical training. The current field of periodontics includes a broad range of surgical skills and technologies to regenerate predictably destroyed tissues and manage complex interdisciplinary treatment that may, in some way, involve the tissues that support teeth and implants. In addition, periodontal researchers have shown that moderate-to-severe periodontitis increases the systemic inflammatory burden and transient bacteremias that result in a significant independent role for periodontitis in multiple systemic diseases. Although many periodontists have very advanced practices that incorporate certain aspects of the current and near-future dimensions of periodontics, the innovations and technologies have not yet fully integrated throughout the specialty. It is an appropriate time to ask the question: Quo vadis? Which paths have the potential to deliver great value to our patients and to the health-care system? And who will be our patients in the near future? We propose some key capabilities, knowledge and clinical applications. Perhaps most importantly, we propose new partnerships. Much of the vision centers around the application of special diagnostic technologies and surgical skills to help our dental colleagues better manage complex dental and periodontal cases and to deliver on the promise of reducing systemic inflammation sufficiently to enhance medical management of certain chronic diseases and reduce preterm births. The specialty has always been about retaining teeth in good health and in recent years has focused on controlling oral inflammation to enhance systemic health. We already have several of the key principles, concepts and technologies that are likely to define the role of periodontics in the evolving health-care delivery system. Perhaps it is time to define the mission and start moving toward the future periodontics.
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Doenças Periodontais/terapia , Periodontia/tendências , Progressão da Doença , Previsões , Humanos , Especialidades Odontológicas/tendênciasRESUMO
Care systems worldwide regularly undergo reforms and adjustments in the hope of system improvements. In many ways this can align with calls for governments to be more 'adaptive' and 'agile' to changing care demands. However, such continued adaptations can create turbulence for the care sectors in question. In this article, we examine the large-scale reform of the Australia National Disability Insurance Scheme and the impact of a series of adaptations on the disability care sector in Australia. We find that the disability sector in Australia is experiencing turbulence and a lack of clarity about the rules regarding the programme, resulting in increased administrative burden and financial pressures. Such turbulence has flow-on effects on the level of care that is able to be accessed by people with disability in Australia.
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Pessoas com Deficiência , Seguro por Deficiência , Austrália , Humanos , PolíticasRESUMO
The National Disability Insurance Scheme (NDIS) in Australia and other similar international movements towards consumer direction have highlighted the importance of including consumers to ensure their service preferences are operationalised. Discrete Choice Experiments (DCEs) are an established method to quantify consumer preferences. The feasibility of using DCEs with people with intellectual disability is largely untested. Consenting participants eligible for disability support services (n = 18) participated in the mixed methods exploratory study. The DCE comprised a series of choices between two hypothetical service providers offering a combination of services relating to social and economic participation (e.g. support with finding and keeping a job), with four levels of service (no service, online support, group support, one to one support). Pictographs and simplified English were used to represent the hypothetical services and levels and a 'think aloud' protocol adopted. Most participants (N = 16, 89%) completed the DCE task. The findings from the think aloud task indicated that some participants were weighing up the options and making decisions based on their goals and personal preferences. However, other participants did not focus on all presented attributes and levels when making a decision; a common 'short-cut' heuristic also observed in DCE tasks with general population participants. Further research including investigating other DCE techniques, such as best-worst scaling, would be beneficial to identify how preference-elicitation tasks can be developed and applied with people with intellectual disabilities to ensure that future service innovations are designed and administered in ways which best meet their needs and preferences.
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Pessoas com Deficiência , Deficiência Intelectual , Comportamento de Escolha , Comportamento do Consumidor , Tomada de Decisões , Humanos , Deficiência Intelectual/terapia , Preferência do PacienteRESUMO
OBJECTIVE: To explore the perceptions of the Australian public regarding Australia's aged care workforce, including their willingness to pay more tax to fund better pay and conditions for aged care workers. METHODS: An online survey was developed and administered to a representative sample of Australian adults (aged ≥18 years) by age group, gender and Australian state. Survey respondents completed a series of attitudinal statements to elicit their perceptions of the value of Australia's aged care workforce and were asked to indicate their willingness to pay additional tax to fund better pay and conditions for aged care workers. Those who gave a positive response were then asked to indicate what percentage of additional tax per year they would be willing to pay to ensure better pay and conditions for aged care workers. RESULTS: A total of 2033 adult respondents completed the survey. A majority (78%) of respondents either 'agreed' or 'strongly agreed' that aged care workers should be paid more. Approximately half of the respondents (50.57%) expressed a willingness to pay more tax to ensure better pay and conditions for aged care workers. The mean willingness to pay was 1.31% additional tax overall, and mean percentage additional tax values were relatively consistent across key socio-demographic indicators. CONCLUSIONS: A majority of the Australian public are in favour of improving the wages and employment conditions of aged care workers. However, only one in two Australians is willing to pay more tax to ensure better pay and conditions for aged care workers.
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Emprego , Salários e Benefícios , Humanos , Adolescente , Adulto , Idoso , Austrália , Inquéritos e Questionários , Pessoal de SaúdeRESUMO
BACKGROUND: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines. Methylation of DNA is an important regulator of gene expression and changes with age. OBJECTIVE: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leucocytes and macrophages. METHODS AND RESULTS: Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) in the TNF promoter in human peripheral blood cells from 312 healthy controls (0.8% per decade, confidence interval (CI)=0.44-1.13%, p=1×10(-5)) and primary monocyte-derived macrophages (MDM) from a separate population of 78 healthy controls (1.4% per decade, CI=0.79-2.13%, p=7×10(-5)). Methylation a TNF promoter fragment (-345-+154) resulted in 78% reduction of reporter gene activity compared with the unmethylated promoter construct. CONCLUSIONS: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator.
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Envelhecimento/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Adulto , Sequência Consenso/genética , Feminino , Expressão Gênica , Genes Reporter , Humanos , Macrófagos/metabolismo , Masculino , Motivos de Nucleotídeos/genética , Fatores de Transcrição/metabolismoRESUMO
This article focuses on the ways in which members of Alcoholics Anonymous and Narcotics Anonymous construct themselves as being in recovery from addiction. In this original study, data were taken from 19 participants. They were analysed using Willig's six-stage Foucauldian discourse analytic method. This method is suited to enabling the analyst to locate discourse resources used by participants within broader, dominant, discourses, and for exploration of the implications of these constructions for subjectivity and practice. This article presents a discussion of analytic findings. Mainstream academia has often constructed 12-Step recovery as a largely totalising discourse. This is likely to have negatively prejudiced health professionals and may help explain relatively low referral rates into 12-Step resources for addicted clients. However, our analysis suggested that participants constructed themselves not as subjected by Alcoholics Anonymous and Narcotics Anonymous discourse, but as drawing on it in ways aligned with agency, in order to practice care of the self in pursuit of various ethical goals. This implies 12-Step recovery to be less antithetical to, and indeed more aligned with, humanistic practitioner values than is perhaps often assumed to be the case. This finding suggests that practitioners may need to consider reappraising their view of 12-Step recovery. The discussion will therefore focus on the agency-structure dialectic that seemed to be at the heart of participant constructions of addiction and recovery. It is also a finding which points to an urgent need for more qualitative studies in the currently under-researched, and hence perhaps poorly understood, area of 12-Step recovery from addiction.
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Alcoolismo , Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Alcoólicos Anônimos , Alcoolismo/terapia , Humanos , Encaminhamento e Consulta , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
OBJECTIVES: Successful implementation of asymptomatic testing programmes using lateral flow tests (LFTs) depends on several factors, including feasibility, acceptability and how people act on test results. We aimed to examine experiences of university students and staff of regular asymptomatic self-testing using LFTs, and their subsequent behaviours. DESIGN AND SETTING: A qualitative study using semistructured remote interviews and qualitative survey responses, which were analysed thematically. PARTICIPANTS: People who were participating in weekly testing feasibility study, between October 2020 and January 2021, at the University of Oxford. RESULTS: We interviewed 18 and surveyed 214 participants. Participants were motivated to regularly self-test as they wanted to know whether or not they were infected with SARS-CoV-2. Most reported that a negative test result did not change their behaviour, but it did provide them with reassurance to engage with permitted activities. In contrast, some participants reported making decisions about visiting other people because they felt reassured by a negative test result. Participants valued the training but some still doubted their ability to carry out the test. Participants were concerned about safety of attending test sites with lots of people and reported home testing was most convenient. CONCLUSIONS: Clear messages highlighting the benefits of regular testing for family, friends and society in identifying asymptomatic cases are needed. This should be coupled with transparent communication about the accuracy of LFTs and how to act on either a positive or negative result. Concerns about safety, convenience of testing and ability to do tests need to be addressed to ensure successful scaling up of asymptomatic testing.
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COVID-19 , Autoteste , Teste para COVID-19 , Humanos , Percepção , SARS-CoV-2 , Estudantes , UniversidadesRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic in 2020, the UK government began a mass severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing program. This study aimed to determine the feasibility and acceptability of organized regular self-testing for SARS-CoV-2. METHODS: This was a mixed-methods observational cohort study in asymptomatic students and staff at University of Oxford, who performed SARS-CoV-2 antigen lateral flow self-testing. Data on uptake and adherence, acceptability, and test interpretation were collected via a smartphone app, an online survey, and qualitative interviews. RESULTS: Across 3 main sites, 551 participants (25% of those invited) performed 2728 tests during a follow-up of 5.6 weeks; 447 participants (81%) completed at least 2 tests, and 340 (62%) completed at least 4. The survey, completed by 214 participants (39%), found that 98% of people were confident to self-test and believed self-testing to be beneficial. Acceptability of self-testing was high, with 91% of ratings being acceptable or very acceptable. A total of 2711 (99.4%) test results were negative, 9 were positive, and 8 were inconclusive. Results from 18 qualitative interviews with students and staff revealed that participants valued regular testing, but there were concerns about test accuracy that impacted uptake and adherence. CONCLUSIONS: This is the first study to assess feasibility and acceptability of regular SARS-CoV-2 self-testing. It provides evidence to inform recruitment for, adherence to, and acceptability of regular SARS-CoV-2 self-testing programs for asymptomatic individuals using lateral flow tests. We found that self-testing is acceptable and people were able to interpret results accurately.
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OBJECTIVE: Genetic variation in the gene for interleukin-6 (IL-6) contributes to the pathogenesis of inflammatory arthritis, but the role, if any, of epigenetic variability has not been reported. The aims of this study were to compare the DNA methylation status of the IL6 promoter in rheumatoid arthritis (RA) patients and control subjects and to study the effects on gene expression. METHODS: Genomic DNA was isolated from peripheral blood mononuclear cells (PBMCs) obtained from RA patients and healthy controls. Macrophages from healthy controls were isolated and stimulated with lipopolysaccharide (LPS). Methylation status was determined using bisulfite genomic sequencing and IL6 messenger RNA (mRNA) levels by quantitative polymerase chain reaction. Gel shift assays were performed with methylated or unmethylated probes and HeLa cell nuclear extract. RESULTS: The proximal CpG motifs (-666 to +27) were predominantly unmethylated and the upstream motifs (-1099 to -1001) were highly methylated in PBMCs from patients and controls. Methylation of individual CpG motifs was similar, except at -1099C, which was less methylated in the patients than in the controls (58% versus 98%; P = 1 x 10(-6)). To test whether this observation might relate to gene regulation, LPS-stimulated macrophages were grouped according to their IL6 mRNA stimulation index (SI). The level of methylation at -1099C was significantly lower in the group with high (SI >75) compared with the group with low (SI <10) induced mRNA levels (71% versus 93%; P = 0.007). Gel shift assays revealed decreased protein binding to the -1099C unmethylated probe. CONCLUSION: These data suggest that methylation of a single CpG in the IL6 promoter region may affect IL6 gene regulation and may play a role in the pathogenesis of RA.
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Artrite Reumatoide/genética , Ilhas de CpG/genética , Metilação de DNA/genética , Interleucina-6/genética , Regiões Promotoras Genéticas/genética , Adulto , Células Cultivadas , Distribuição de Qui-Quadrado , Ensaio de Desvio de Mobilidade Eletroforética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Leucócitos Mononucleares/fisiologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
Personalisation schemes and associated markets for social care have been a growing trend in industrialised countries over recent decades. While there is no single approach to marketisation of social care and personalisation, often funds are devolved to clients of care services to be used to purchase services directly from market. Such arrangements are vulnerable to market failures and 'thin' markets, causing the need for stewardship of the social care markets. We present findings from a 2018 survey of 626 care service providers in the Australian National Disability Insurance Scheme market on their experience of market conditions. Over 46% of respondents listed 'addressing pricing' as their top action for addressing market problems. Qualitative findings show that central price setting is detached from service delivery realities, affecting service quality and capability building potential. We argue that devolution of price setting to, or at least flexibility and discretion at, the local level is likely to be a key to solving pricing dilemmas in personalisation schemes.
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Comércio , Pessoas com Deficiência , Acessibilidade aos Serviços de Saúde/economia , Austrália , Fortalecimento Institucional , Pessoas com Deficiência/estatística & dados numéricos , Humanos , Política Pública , Inquéritos e QuestionáriosRESUMO
Family-based analysis has revealed several loci for psoriasis and the locus, PSORS5, on chromosome 3q21 has been found in two independent studies. In this region, cystatin A (CSTA) encodes a skin barrier cystein protease inhibitor found in human sweat and it is over-expressed in psoriatic skin. Three CSTA markers at positions -190 (g.-190T>C), +162 (c.162T>C) and +344 (c.344C>T) were analysed in 107 unrelated patients and 216 matched controls. There was a significant trend for association with CSTA c.162T>C and psoriasis (odds ratio (OR)=3.45, P<0.001). Analysis of constructed haplotypes showed a highly significant association between disease and CSTA -190T/+162C/+344C (CSTA TCC) (P=10(-6)). In independent study, a TDT analysis in 126 nuclear families confirmed the over-transmission of CSTA TCC (P=0.0001). The presence of statistical interaction between CSTA TCC haplotype and HLA-Cw6 at PSORS1 locus was detected by performing TDT analysis on CSTA haplotypes stratified by the presence or absence of the risk allele at HLA-Cw6 locus. To estimate the disease risk we employed conditional logistic regression on the family data. The CSTA TCC haplotype is only associated with psoriasis in those individuals carrying the risk allele at the HLA-Cw6 locus (OR=2.22, P=0.0004, 95% CI= 1.42, 3.49). These results represent a major step towards the dissection of genetic factors involved in the pathogenesis of psoriasis.
Assuntos
Cistatinas/genética , Antígenos HLA-C/genética , Psoríase/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 6/genética , Cistatina A , Cistatinas/metabolismo , Família , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA-C/metabolismo , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Psoríase/imunologia , Psoríase/metabolismoRESUMO
Interleukin-1beta (IL-1beta) activates inflammatory mediator cascades and has been implicated in the pathogenesis of several diseases. Single nucleotide polymorphisms (SNPs) of the IL1B promoter have been associated with various inflammatory diseases. We recently reported that IL1B gene transcription was influenced by four promoter SNPs, and that individual SNP function in vitro was governed by haplotype context. In the present study we tested the in vivo relevance of this observation by comparing IL1B promoter haplotype-pairs with IL-1beta protein levels in 900 gingival tissue fluid samples. Three SNPs (-511, -1464, -3737) defined four IL1B promoter haplotypes that occurred in the study population and could be assigned unambiguously to each chromosome. The four haplotypes defined ten haplotype-pairs of which four pairs, representing 57% of the population, were associated with 28-52% higher IL-1beta protein levels in vivo. Two of these pairs, characterized by homozygosity for the common allele at -3737, were also associated with raised serum levels of C-reactive protein (p = 0.02). We validated these findings in stimulated peripheral blood mononuclear cells (PBMCs) from a separate population (N = 70). PBMCs with IL1B haplotype-pairs associated with higher in vivo levels of IL-1beta produced 86-287% more IL-1beta in vitro than the reference group. We believe that this is the first demonstration of a relationship between in vivo levels of an inflammatory mediator and gene promoter haplotypes on both chromosomes. These findings may apply to other inducible genes and could provide a logical framework for exploring disease risk related to genetic variability in pathogenic mediators.
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Proteína C-Reativa/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Regiões Promotoras Genéticas , Idoso , Alelos , Estudos de Coortes , Feminino , Dosagem de Genes , Gengiva/metabolismo , Haplótipos , Homozigoto , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Anormalidades Induzidas por Medicamentos/história , Antieméticos/história , Talidomida/história , Anormalidades Induzidas por Medicamentos/etiologia , Antieméticos/efeitos adversos , Controle de Medicamentos e Entorpecentes/história , Controle de Medicamentos e Entorpecentes/legislação & jurisprudência , História do Século XX , Humanos , Recém-Nascido , Talidomida/efeitos adversos , Reino Unido , Estados UnidosRESUMO
BACKGROUND: Twin studies have suggested some genetic predisposition to alcoholic liver disease (ALD). Cytokines may be involved in ALD pathogenesis. Several cytokine genes contain functionally significant polymorphisms. Associations between ALD and polymorphisms on the interleukin-1 (IL-1), IL-10, and tumor necrosis factor-alpha (TNF-alpha) genes have been reported but not confirmed. OBJECTIVE: Comparison of allelic frequencies of cytokine gene polymorphisms between 223 patients with decompensated ALD (a more severe phenotype than in previous studies) and 162 controls with similar lifetime alcohol consumption but without serious liver disease. METHODS: Genotyping of polymorphisms of the genes for IL-1A (+4,845), IL-1B (+3,954 and -511), IL-1 receptor antagonist (+2,018), IL-6 (-174), IL-10 (-574 and -1,117), and TNF-alpha (-238 and -308). RESULTS: There were increases with respect to IL-6 -174 (2 x 3 chi(2)P < 0.1, OR for G allele carriage 1.61[1.05-2.48]) and Il-10 -592 (2 x 3 chi(2) 7.90, P < 0.01, OR for AA genotype carriage 4.85[1.40-16.8]) polymorphisms in patients compared with heavy-drinking controls. Differences were greater with analysis confined to Child's C patients. Genotype distribution for the other seven polymorphisms did not differ significantly between patients and heavy-drinking controls. CONCLUSION: These data are consistent with a modest role for IL-6 -174, and IL-10 -592 polymorphisms in genetic susceptibility to ALD.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Citocinas/genética , Hepatopatias Alcoólicas/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-10/genética , Interleucina-6/genética , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
For many chronic diseases, the influence of genetics is complex and phenotypes do not conform to simple Mendelian patterns of inheritance. Discussed here are two types of genetic influences on healthy aging. The first involves variation in the gene sequence itself and how this may influence disease susceptibility, progression, and severity, interacting with other recognized risk factors. The second involves epigenetic regulatory mechanisms that may potentially provide insight into how environmental influences affect the expressed genome, thus improving our understanding of the genetic mechanisms underlying multifactorial diseases. The interleukin-1 family of cytokines can be used to illustrate how genetic sequence variation may affect such diseases. This cytokine family plays a key role in mediating inflammation, which is now understood to be a central component of a growing number of chronic diseases. Recent work has revealed many sequence variations in the regulatory DNA of genes encoding important members of the interleukin-1 family, and these variations are associated with differential effects on the inflammatory response. The interactions of environmental factors with both DNA sequence variations and epigenetic modifications are likely to determine the phenotypes of multifactorial diseases of aging as well as the phenotype of healthy aging.
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Envelhecimento/genética , Epigênese Genética , Predisposição Genética para Doença , Inflamação/genética , Interleucina-1/genética , Envelhecimento/fisiologia , Progressão da Doença , Suscetibilidade a Doenças , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1/metabolismo , Fatores de RiscoRESUMO
For many chronic diseases, the influence of genetics is subtle and complex and does not conform to simple Mendelian patterns of inheritance as is seen with single-gene disorders. Genetic variation can influence the propensity for the initiating event, the progression to a clinical disease state, and the trajectory of disease. One example of how genetic variations may affect complex diseases is provided by the interleukin 1 family of cytokines. This cytokine family plays a key role in mediating inflammation, which is a central component of many chronic diseases, including coronary artery disease and rheumatoid arthritis. Recent research has identified many sequence variations in the regulatory DNA of the genes coding for important members of the interleukin 1 family, and these variations are associated with differential effects on the inflammatory response. These in turn alter the risk of some diseases in which inflammation plays a role and also affect physiologic responses, such as the inflammatory response to exercise. As this new genetic knowledge is developed and extended, it may be possible to make health care interventions at an earlier stage, before clinical disease is established, rather than after tissues have been permanently damaged.
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Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Variação Genética , Mediadores da Inflamação/metabolismo , Inflamação/genética , Interleucina-1/genética , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Doença Crônica , Progressão da Doença , Expressão Gênica , Predisposição Genética para Doença , Haplótipos , Humanos , Camundongos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Psoriasis is a chronic inflammatory skin disease that affects 0.1%-5% depending on the population. PSORS1 is the major susceptibility locus, accounting for approximately 33%-50% of the genetic component of psoriasis among Caucasians. PSORS1 is located within the major histocompatibility complex (MHC) locus on 6p21.3. Its position has been refined to hundreds of kilobase and the region located at approximately 100-200 kb telomeric to human leukocyte antigen (HLA)-C is a very strong candidate. To determine the MHC psoriasis risk haplotype, we screened the whole 46 kb interval for single-nucleotide polymorphisms (SNP) and identified 138 SNP. We genotyped 29 SNP throughout this region in psoriatic nuclear families. We calculated the frequency of haplotypes generated by the 29 SNP using all genotyped founder individuals and found four common haplotype with frequency >0.10. We then used SNPtagger to derive the best six SNP and fed these into Transmit using 148 nuclear families. We found that CTGGAC haplotype is a single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27 (p<0.0001). Most importantly the six selected SNP accurately tagged the most common haplotype found in this region. Moreover, using the same program (Transmit) we show that the association with CTGGAC is higher than the one with HLA-Cw6 (chi2=10.53; p=0.0051). Our results give scores as high as the highest single-point scores suggesting that it is unlikely to be able to discriminate the origin of the association on this analysis on strength of association.
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Antígenos HLA-C/genética , Psoríase/etnologia , Psoríase/genética , Telômero/genética , População Branca/genética , Sequência de Bases , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Complexo Principal de Histocompatibilidade/genética , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: Genetically determined variation in proinflammatory cytokine release influences severity of meningococcal disease and other serious infections. OBJECTIVE: To ascertain the relative frequencies of single nucleotide polymorphisms within the interleukin-1 gene locus among patients who survived and those who died of meningococcal disease and a control population of blood donors. DESIGN: Association study. SETTING: England and Wales. PATIENTS: 1106 consecutively received blood samples from persons with microbiologically confirmed meningococcal disease and 839 samples from blood donors. MEASUREMENTS: Patient demographic and outcome data, infecting meningococcal serogroups, and genotype at the IL1B(-511) and IL1RN(+2018) loci of patients and blood donor controls. RESULTS: Genotype frequency did not differ between patients with meningococcal disease and blood donor controls. Logistic regression analysis revealed that the likelihood of death was significantly influenced by age but not socioeconomic status and was higher in patients who were infected with serogroup C (odds ratio for survival, 0.50 [95% CI, 0.33 to 0.78]). Patients carrying the common allele at IL1B(-511) were more likely to survive (odds ratio, 2.01 [CI, 1.11 to 3.79]). Patients with this allele were less likely to survive if they also carried the rare allele at IL1RN(+2018) (odds ratio, 0.61 [CI, 0.38 to 0.993]). CONCLUSION: Genotype at the interleukin-1 gene locus influences likelihood of survival of meningococcal disease but has no effect on susceptibility to the infection. Increasing age and infection with serogroup C also influence the likelihood of death.
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Variação Genética , Interleucina-1/genética , Infecções Meningocócicas/genética , Sialoglicoproteínas/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Pré-Escolar , Inglaterra/epidemiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Proteína Antagonista do Receptor de Interleucina 1 , Infecções Meningocócicas/mortalidade , Pessoa de Meia-Idade , Fatores Socioeconômicos , País de Gales/epidemiologiaRESUMO
BACKGROUND: There is disagreement as to whether patient stratification by a combination of diabetes, smoking, and genetic test results is useful for informing the frequency of dental prophylaxes. METHODS: The authors appeal to basic tenets of clinical study design and statistical analysis of clinical investigations, and highlight how secondary ad hoc analyses, such as those of Diehl and colleagues, are frequently underpowered and inconclusive. They also provide evidence from numerous studies supporting the use of genetics to identify risk. RESULTS: The authors believe the conclusions reached from their original analyses are valid and the analyses of Diehl and colleagues serve to simply reinforce the authors' specific intent of avoiding such underpowered analyses altogether with the Michigan Personalized Prevention Study. CONCLUSIONS: Until full genome sequencing in many people with highly specified disease phenotypes is feasible, experimental approaches based on biological findings and hypothesis testing should not be summarily discounted. PRACTICAL IMPLICATIONS: Stratification of patients to provide "personalized" treatment remains an important, yet elusive, goal. The current debate serves to highlight the need for large, clinical utility studies that can adequately determine how phenotypic and genotypic data can be best used to improve oral health in the US population.
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Predisposição Genética para Doença/genética , Odontologia Preventiva/estatística & dados numéricos , Adulto , Assistência Odontológica/estatística & dados numéricos , Cárie Dentária/etiologia , Cárie Dentária/genética , Cárie Dentária/prevenção & controle , Testes Genéticos , Humanos , Interleucina-1/genética , Periodontite/etiologia , Periodontite/genética , Periodontite/prevenção & controle , Odontologia Preventiva/métodos , Fatores de RiscoRESUMO
UNLABELLED: Genetic factors may influence implant failure caused by osteolysis after THA. In an association study of 481 subjects after THA, we found that carriage of the TNF-238A allele was associated with an increased incidence of osteolysis versus noncarriage (odds ratio, 1.7) and was independent of other risk factors. Genetic and environmental factors influence implant survival after THA. INTRODUCTION: Tumor necrosis factor (TNF) is thought to play a role in osteolysis, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at -238 and -308 in the TNF gene promoter are associated with differences in susceptibility to several TNF-mediated diseases. We tested whether these polymorphisms are associated with osteolysis after THA. MATERIALS AND METHODS: A total of 481 whites (214 with failed versus 267 with intact implants) were recruited 11.7 +/- 4 years after cemented THA. Genomic DNA was extracted from peripheral blood and genotyped for the -238 and -308 polymorphisms using the Taqman 5' nuclease method. Healthy controls (n = 500) from the background population were also genotyped to establish the local prevalence of these alleles. RESULTS: The carriage of -238A was 8.8% in the background population and 10.9% in the THA controls (p > 0.05). Carriage of -238A in the osteolysis group was 17.3% (odds ratio, 1.7; 95% CI, 1.0-2.9). Carriage was highest (20.5%) in patients with more widespread osteolysis (OR, 2.1; 1.2-3.8). The association of -238A with osteolysis was independent of other risk factors for osteolysis (logistic regression analysis: OR, 1.8; 1.0-3.2). Carriage of -308A was not associated with osteolysis. CONCLUSION: Genetic, as well as environmental factors, influence implant failure after THA. Whether the TNF-238 polymorphism causes a biological change that predisposes to loosening or is in linkage disequilibrium with such a locus is not yet known.