Dental plaque as a biofilm and a microbial community – implications for health and disease

Dental plaque is a structurally- and functionally-organized biofilm. Plaque forms in an ordered way and has a diverse microbial composition that, in health, remains relatively stable over time (microbial homeostasis). The predominant species from diseased sites are different from those found in healthy sites, although the putative pathogens can often be detected in low numbers at normal sites. In dental caries, there is a shift toward community dominance by acidogenic and acid-tolerating species such as mutans streptococci and lactobacilli, although other species with relevant traits may be involved. Strategies to control caries could include inhibition of biofilm development (e.g. prevention of attachment of cariogenic bacteria, manipulation of cell signaling mechanisms, delivery of effective antimicrobials, etc.), or enhancement of the host defenses. Additionally, these more conventional approaches could be augmented by interference with the factors that enable the cariogenic bacteria to escape from the normal homeostatic mechanisms that restrict their growth in plaque and out compete the organisms associated with health. Evidence suggests that regular conditions of low pH in plaque select for mutans streptococci and lactobacilli. Therefore, the suppression of sugar catabolism and acid production by the use of metabolic inhibitors and non-fermentable artificial sweeteners in snacks, or the stimulation of saliva flow, could assist in the maintenance of homeostasis in plaque. Arguments will be presented that an appreciation of ecological principles will enable a more holistic approach to be taken in caries control

Statistical decadal predictions for sea surface temperatures: a benchmark for dynamical GCM predictions

Accurate decadal climate predictions could be used to inform adaptation actions to a changing climate. The skill of such predictions from initialised dynamical global climate models (GCMs) may be assessed by comparing with predictions from statistical models which are based solely on historical observations. This paper presents two benchmark statistical models for predicting both the radiatively forced trend and internal variability of annual mean sea surface temperatures (SSTs) on a decadal timescale based on the gridded observation data set HadISST. For both statistical models, the trend related to radiative forcing is modelled using a linear regression of SST time series at each grid box on the time series of equivalent global mean atmospheric CO2 concentration. The residual internal variability is then modelled by (1) a first-order autoregressive model (AR1) and (2) a constructed analogue model (CA). From the verification of 46 retrospective forecasts with start years from 1960 to 2005, the correlation coefficient for anomaly forecasts using trend with AR1 is greater than 0.7 over parts of extra-tropical North Atlantic, the Indian Ocean and western Pacific. This is primarily related to the prediction of the forced trend. More importantly, both CA and AR1 give skillful predictions of the internal variability of SSTs in the subpolar gyre region over the far North Atlantic for lead time of 2 to 5 years, with correlation coefficients greater than 0.5. For the subpolar gyre and parts of the South Atlantic, CA is superior to AR1 for lead time of 6 to 9 years. These statistical forecasts are also compared with ensemble mean retrospective forecasts by DePreSys, an initialised GCM. DePreSys is found to outperform the statistical models over large parts of North Atlantic for lead times of 2 to 5 years and 6 to 9 years, however trend with AR1 is generally superior to DePreSys in the North Atlantic Current region, while trend with CA is superior to DePreSys in parts of South Atlantic for lead time of 6 to 9 years. These findings encourage further development of benchmark statistical decadal prediction models, and methods to combine different predictions

Efficacy of a family practice-based lifestyle intervention program to increase physical activity and reduce clinical and physiological markers of vascular health in patients with high normal blood pressure and/or high normal blood glucose (SNAC): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous interventions to increase physical activity and reduce cardiovascular risk factors have been targeted at individuals with established disease; less attention has been given to intervention among individuals with high risk for disease nor has there been determination of the influence of setting in which the intervention is provided. In particular, family practice represents an ideal setting for the provision and long-term maintenance of lifestyle interventions for patients at risk (ie high-normal blood pressure or impaired glucose tolerance).</p> <p>Methods/design</p> <p>The Staged Nutrition and Activity Counseling (SNAC) study is a randomized clustered design clinical trial that will investigate the effectiveness and efficacy of a multi-component lifestyle intervention on cardiovascular disease risk factors and vascular function in patients at risk in primary care. Patients will be randomized by practice to either a standard of care lifestyle intervention or a behaviourally-based, matched prescriptive physical activity and diet change program. The primary goal is to increase physical activity and improve dietary intake according to Canada's Guides to Physical Activity Healthy Eating over 24 months. The primary intention to treat analysis will compare behavioral, physiological and metabolic outcomes at 6, 12 and 24 months post-randomization including estimation of incident hypertension and/or diabetes.</p> <p>Discussion</p> <p>The design features of our trial, and the practical problems (and solutions) associated with implementing these design features, particularly those that result in potential delay between recruitment, baseline data collection, randomization, intervention, and assessment will be discussed. Results of the SNAC trial will provide scientific rationale for the implementation of this lifestyle intervention in primary care.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN:42921300">ISRCTN:42921300</a></p

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10−8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10−17; rs715 at 2q34, P = 9.97 × 10−14; rs477992 at 1p12, P = 2.60 × 10−12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10−6) and serine (P = 2.48 × 10−4) between MacTel cases and controls

The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity

Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from opportunistic pathogens

Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders

Effect of diazepam on temporomandibular joints in rats with increased occlusal vertical dimension

Anxiolytic agents, mainly benzodiazepines, have been used to treat symptomatic disorders of the temporomandibular joint (TMJ). Our aim was to evaluate the effect of diazepam on the TMJ of rats with increased occlusal vertical dimension (iOVD). Forty male rats were randomly assigned to 4 groups: control rats were given sham iOVD plus saline solution daily for 7 days. The first experimental group was given sham iOVD plus diazepam 2.5 mg/kg/intramuscularly daily for 7 days (diazepam alone group); the second had iOVD induced in molars for 7 days plus saline daily for 7 days (iOVD alone group); and the third had iOVD induced in molars for 7 days plus diazepam 2.5 mg/kg/intramuscularly daily for 7 days (iOVD plus diazepam group). At the end of each experiment the animals were killed and their bilateral TMJs were removed, randomly stained with haematoxylin and eosin and sirius-red, and immunoassayed. The thickness of condylar cartilage and of fibrous, proliferating, mature, and hypertrophic layers, number of collagen fibres, and the articular area were measured. Proinflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumour necrosis factor (TNE)-alpha) were also measured. ANOVA and Tukey's tests or the Kruskal-Wallis test were used to compare data among groups (alpha = 5%). Condylar cartilage was thicker in the control group than in the other groups, the diazepam alone group being thicker than the other 2 experimental groups. There were fewer collagen fibres in the 2 groups given diazepam than in the other 2 groups, and there were no significant differences in the area of cartilage among groups. The controls had lower concentrations of all cytokines (p<0.05) than the 3 experimental groups, except for IL-6. Both iOVD groups had higher concentrations of IL-1 alpha, IL-1 beta, and IL-6 than the diazepam alone group. Diazepam alone was associated with increased concentrations of all cytokines except IL-6. We conclude that both iOVD and diazepam induced significant changes in rats' articular cartilage. (C) 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.52543844