Evidence - Based Dentistry: Do We Know What It Means?

Da bi obavljao posao na način stomatologije zasnovane na dokazu praktičar mora biti sposoban i pripravan oblikovati jasno pitanje, uspješno pronaći pouzdan dokaz, sustavno ispitati dokaz te, ako je važan i vjerodostojan, primijeniti rezultate procjene u svojoj praksi. Materijali, instrumenti, tehnike i terapije mijenjaju se tako brzo da mnogi od nas imaju teškoće s pamćenjem njihovih imena, a napose s pojedinostima njihove uporabe. Širenjem elektroničke tehnologije (internet, CD-ROM i DVD) znatno je lakše pronaći informacije. U mnogo slučaja pacijenti imaju isti pristup podatcima kao i liječnici, pa kako njihove razine znanja rastu, tako rastu njihova očekivanja i zahtjevi. Stomatologija zasnovana na dokazu zatvara pukotinu između kliničkog istraživanja i stvarnoga svijeta stomatološke prakse te stomatolozima daje moćne alate za interpretaciju i primjenu nalaza istraživanja. Stomatologija zasnovana na dokazu je proces koji nije rigidno metodološko ispitivanje znanstvenoga dokaza kojim se diktira što bi praktičari trebali ili ne bi trebali obavljati. U prvome redu to je proces utemeljen na integriranju znanstvene baze za kliničku skrb uporabom temeljitih, nepristranih pregleda i najpouzdanijega znanstvenoga dokaza u bilo kojem trenutku s kliničkim čimbenicima i čimbenikom pacijenta kako bi se na najbolji mogući način donijele odluke o prikladnoj zdravstvenoj skrbi za specifične kliničke okolnosti. Stomatologija zasnovana na dokazu oslanja se na ulogu pojedinačne stručne prosudbe u tome procesu.To practice in an evidence-based dentistry manner, practitioners must be able to formulate a clear question, find the best available evidence efficiently, evaluate the evidence systematically and, if it is relevant and credible, apply the results of the appraisal to their practice. Materials, instruments, techniques, and therapies change so fast that most of us have difficulty keeping up with their names, much less the details of their use. As electronic technology (Internet, CD-ROM, and DVD) expands, information retrieval is increasingly easy. Patients have access to the same data that doctors do in many cases, and as their knowledge levels increase, so do their expectations and demands. Evidence-based dentistry closes the gap between clinical research and real world dental practice and provides dentists with powerful tools to interpret and apply research findings. Evidence-based dentistry process is not a rigid methodological evaluation of scientific evidence that dictates what practitioners should or should not do. Rather, the evidencebased dentistry process is based on integrating the scientific basis for clinical care, using thorough, unbiased reviews and the best available scientific evidence at any one time, with clinical and patient factors to make the best possible decision(s) about appropriate health care for specific clinical circumstances. Evidence-based dentistry relies on the role of individual professional judgment in this process

Immunoglobulin κ Chain Allotypes (KM) in Onchocerciasis

GM and KM allotypes, powerful tools for genetic characterization of human populations, have been shown to play an important role in genetic predisposition to some infectious diseases. Two diverse racial groups-Afro-Ecuadorians and Amerindians-living in a single restricted geographical area of Ecuador, appear to have different risk factors for acquisition and clinical expression of onchocerciasis, a disease caused by the filarial parasite Onchocerca volvulus. In this study, GM and KM allotypes were determined in 25 Afro-Ecuadorians and 24 Amerindians infected with Onchocerca volvulus (INF) and in putative immune individuals (PI). In Afro-Ecuadorians, the frequency of the homozygous KM 3 phenotype was significantly decreased in INF as compared with the PI group (20 vs. 68%; P = 0.0012), while the frequency of the heterozygous KM 1,3 phenotype was increased in INF as compared with the PI subjects (48 vs 9%; P = 0.0044). These results suggest that in Afro- Ecuadorians KM 3 is associated with a lower relative risk (resistance), whereas KM 1,3 is associated with an increased risk (susceptibility) of onchocerciasis

Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats.

KEY POINTS: Exposure to chronic hypoxia during gestation influences long-term health and development, including reproductive capacity, across generations. If the peri-conceptual environment in the developing oviduct is affected by gestational hypoxia, then this could have implications for later fertility and the health of future generations. In the present study, we show that the oviducts of female rats exposed to chronic hypoxia in utero have reduced telomere length, decreased mitochondrial DNA biogenesis and increased oxidative stress The results of the present study show that exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in early adulthood and they help us understand how exposure to hypoxia during development could influence reproductive health across generations. ABSTRACT: Exposure to chronic hypoxia during fetal development has important effects on immediate and long-term outcomes in offspring. Adverse impacts in adult offspring include impairment of cardiovascular function, metabolic derangement and accelerated ovarian ageing. However, it is not known whether other aspects of the female reproductive system may be similarly affected. In the present study, we examined the impact of chronic gestational hypoxia on the developing oviduct. Wistar rat dams were randomized to either normoxia (21%) or hypoxia (13%) from day 6 post-mating until delivery. Post-delivery female offspring were maintained in normoxia until 4 months of age. Oviductal gene expression was assayed at the RNA (quantitative RT-PCR) and protein (western blotting) levels. Oviductal telomere length was assayed using Southern blotting. Oviductal telomere length was reduced in the gestational hypoxia-exposed animals compared to normoxic controls (P < 0.01). This was associated with a specific post-transcriptional reduction in the KU70 subunit of DNA-pk in the gestational hypoxia-exposed group (P < 0.05). Gestational hypoxia-exposed oviducts also showed evidence of decreased mitochondrial DNA biogenesis, reduced mtDNA copy number (P < 0.05) and reduced gene expression of Tfam (P < 0.05) and Pgc1α (P < 0.05). In the hypoxia-exposed oviducts, there was upregulation of mitochondrial-specific anti-oxidant defence enzymes (MnSOD; P < 0.01). Exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in adulthood. The oviduct plays a central role in early development as the site of gamete transport, syngamy, and early development; hence, accelerated ageing of the oviductal environment could have important implications for fertility and the health of future generations

A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13

SummaryObesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.PaperCli

Selected Toll-like Receptor Ligands and Viruses Promote Helper-Independent Cytotoxic T Cell Priming by Upregulating CD40L on Dendritic Cells

SummaryCD40L (CD154) on CD4+ T cells has been shown to license dendritic cells (DCs) via CD40 to prime cytotoxic T lymphocyte (CTL) responses. We found that the converse (CD40L on DCs) was also important. Anti-CD40L treatment decreased endogenous CTL responses to both ovalbumin and influenza infection even in the absence of CD4+ T cells. DCs expressed CD40L upon stimulation with agonists to Toll-like receptor 3 (TLR3) and TLR9. Moreover, influenza infection, which stimulates CTLs without help, upregulated CD40L on DCs, but herpes simplex infection, which elicits CTLs through help, did not. CD40L-deficient (Cd40lg−/−) DCs are suboptimal both in vivo in bone marrow chimera experiments and in vitro in mixed lymphocyte reactions. In contrast, Cd40lg−/− CD8+ T cells killed as effectively as wild-type cells. Thus, CD40L upregulation on DCs promoted optimal priming of CD8+ T cells without CD4+ T cells, providing a mechanism by which pathogens may elicit helper-independent CTL immunity

Rapid reduction versus abrupt quitting for smokers who want to stop soon: a randomised controlled non-inferiority trial

Background: The standard way to stop smoking is to stop abruptly on a quit day with no prior reduction in consumption of cigarettes. Many smokers feel that reduction is natural and if reduction programmes were offered, many more might take up treatment. Few trials of reduction versus abrupt cessation have been completed. Most are small, do not use pharmacotherapy, and do not meet the standards necessary to obtain a marketing authorisation for a pharmacotherapy.\ud Design/Methods: We will conduct a non-inferiority andomised trial of rapid reduction versus standard abrupt cessation among smokers who want to stop smoking. In the reduction arm,participants will be advised to reduce smoking consumption by half in the first week and to 25% of baseline in the second, leading up to a quit day at which participants will stop smoking completely.This will be assisted by nicotine patches and an acute form of nicotine replacement therapy. In the abrupt arm participants will use nicotine patches only, whilst smoking as normal, for two weeks prior to a quit day, at which they will also stop smoking completely. Smokers in either arm will have standard withdrawal orientated behavioural support programme with a combination of nicotine patches and acute nicotine replacement therapy post-cessation.\ud Outcomes/Follow-up: The primary outcome of interest will be prolonged abstinence from smoking, with secondary trial outcomes of point prevalence, urges to smoke and withdrawal\ud symptoms. Follow up will take place at 4 weeks, 8 weeks and 6 months post-quit day

Demographic and biologic influences on survival in whites and blacks: 40 years of follow-up in the Charleston heart study

BACKGROUND: In the United States, life expectancy is significantly lower among blacks than whites. We examined whether socioeconomic status (SES) and cardiovascular disease (CVD) risk factors may help explain this disparity. METHODS: Forty years (1961 through 2000) of all-cause mortality data were obtained on a population-based cohort of 2,283 subjects in the Charleston Heart Study (CHS). We examined the influence of SES and CVD risk factors on all-cause mortality. RESULTS: Complete data were available on 98% of the original sample (647 white men, 728 white women, 423 black men, and 443 black women). After adjusting for SES and CVD risk factors, the hazard ratios (HRs) for white ethnicity were 1.14 (0.98 to 1.32) among men and 0.90 (0.75 to 1.08) among women, indicating that the mortality risk was 14% greater for white men and 10% lower for white women compared to their black counterparts. However the differences were not statistically significant. CONCLUSION: While there are marked contrasts in mortality among blacks and whites in the CHS, the differences can be largely explained by SES and CVD risk factors. Continued focus on improving and controlling cardiovascular disease risk factors may reduce ethnic disparities in survival

4. Farmland Conservation

Expert assessors Lynn V. Dicks, University of Cambridge, UK Ian Hodge, University of Cambridge, UK Clunie Keenleyside, Institute for European Environmental Policy, UK Will Peach, Royal Society for the Protection of Birds, UK Nicola Randall, Harper Adams University, UK Jörn Scharlemann, United Nations Environment Programme — World Conservation Monitoring Centre, UK Gavin Siriwardena, British Trust for Ornithology, UK Henrik Smith, Lund University, Sweden Rebecca K. Smith, University of Cambrid..

Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology.

BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci. CONCLUSIONS: We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects. Circ Genom Precis Med 2018 Feb; 11(2):e001813