Radiation-induced root surface caries restored with glass-ionomer cement placed in conventional and ART cavity preparations: Results at two years

The document attached has been archived with permission from the Australian Dental Association (8th Jan 2008). An external link to the publisher’s copy is included.Background: There are no published studies comparing the clinical performances of more-viscous glass-ionomer cement (GIC) restorations when placed using conventional and atraumatic restorative treatment (ART) cavity preparation methods to restore root surface caries. Methods: One dentist used encapsulated Fuji IX GP and Ketac-Molar to restore 72 conventional and 74 ART cavity preparations for 15 patients who had received cervicofacial radiation therapy. Two assessors evaluated the restorations at six, 12, and 24 months for retention, marginal defects and surface wear, and recurrent caries. Results: After two years, the cumulative restoration successes were 65.2 per cent for the conventional and 66.2 per cent for the ART cavity preparations, without statistical or clinical significance (P>0.50). Restoration dislodgement accounted for 82.8 per cent and marginal defects for 17.2 per cent of all failures. There were no instances of unsatisfactory restoration wear or recurrent caries observed. Teeth with three or more restored cervical surfaces accounted for 79.3 per cent of all failures (P<0.0001). Conclusions: For root surface caries restored with GIC, the use of hand instruments only with the ART method was an equally effective alternative to conventional rotary instrumentation for cavity preparation. Larger restorations had higher failures, usually from dislodgement.JY Hu, XC Chen, YQ Li, RJ Smales and KH Yi

Toward Fulfilling the Promise of Molecular Medicine in Fragile X

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. It is caused by loss of expression of the fragile X mental retardation protein (FMRP), an RNA-binding protein that negatively regulates protein synthesis. In neurons, multiple lines of evidence suggest that protein synthesis at synapses is triggered by activation of group 1 metabotropic glutamate receptors (Gp1 mGluRs) and that many functional consequences of activating these receptors are altered in the absence of FMRP. These observations have led to the theory that exaggerated protein synthesis downstream of Gp1 mGluRs is a core pathogenic mechanism in FXS. This excess can be corrected by reducing signaling by Gp1 mGluRs, and numerous studies have shown that inhibition of mGluR5, in particular, can ameliorate multiple mutant phenotypes in animal models of FXS. Clinical trials based on this therapeutic strategy are currently under way. FXS is therefore poised to be the first neurobehavioral disorder in which corrective treatments have been developed from the bottom up: from gene identification to pathophysiology in animals to novel therapeutics in humans. The insights gained from FXS and other autism-related single-gene disorders may also assist in identifying molecular mechanisms and potential treatment approaches for idiopathic autism.Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)National Institute of Mental Health (U.S.)FRAXA Research Foundatio

Developing a provisional, international Minimal Dataset for Juvenile Dermatomyositis: for use in clinical practice to inform research.

Juvenile dermatomyositis (JDM) is a rare but severe autoimmune inflammatory myositis of childhood. International collaboration is essential in order to undertake clinical trials, understand the disease and improve long-term outcome. The aim of this study was to propose from existing collaborative initiatives a preliminary minimal dataset for JDM. This will form the basis of the future development of an international consensus-approved minimum core dataset to be used both in clinical care and inform research, allowing integration of data between centres

Recent advances in electronic structure theory and their influence on the accuracy of ab initio potential energy surfaces

Recent advances in electronic structure theory and the availability of high speed vector processors have substantially increased the accuracy of ab initio potential energy surfaces. The recently developed atomic natural orbital approach for basis set contraction has reduced both the basis set incompleteness and superposition errors in molecular calculations. Furthermore, full CI calculations can often be used to calibrate a CASSCF/MRCI approach that quantitatively accounts for the valence correlation energy. These computational advances also provide a vehicle for systematically improving the calculations and for estimating the residual error in the calculations. Calculations on selected diatomic and triatomic systems will be used to illustrate the accuracy that currently can be achieved for molecular systems. In particular, the F+H2 yields HF+H potential energy hypersurface is used to illustrate the impact of these computational advances on the calculation of potential energy surfaces

Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells

One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood–brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment

Parameter estimation for robust HMM analysis of ChIP-chip data

Tiling arrays are an important tool for the study of transcriptional activity, protein-DNA interactions and chromatin structure on a genome-wide scale at high resolution. Although hidden Markov models have been used successfully to analyse tiling array data, parameter estimation for these models is typically ad hoc. Especially in the context of ChIP-chip experiments, no standard procedures exist to obtain parameter estimates from the data. Common methods for the calculation of maximum likelihood estimates such as the Baum-Welch algorithm or Viterbi training are rarely applied in the context of tiling array analysis. Results: Here we develop a hidden Markov model for the analysis of chromatin structure ChIP-chip tiling array data, using t emission distributions to increase robustness towards outliers. Maximum likelihood estimates are used for all model parameters. Two different approaches to parameter estimation are investigated and combined into an efficient procedure. Conclusion: We illustrate an efficient parameter estimation procedure that can be used for HMM based methods in general and leads to a clear increase in performance when compared to the use of ad hoc estimates. The resulting hidden Markov model outperforms established methods like TileMap in the context of histone modification studies.13 page(s

Contraceptive methods and use by women aged 35 and over: A qualitative study of perspectives

<p>Abstract</p> <p>Background</p> <p>More than 30% of the pregnancies in women aged 35 and over are unintended. This paper compares perceptions about contraceptive methods and use among women with and without an unintended pregnancy after turning age 35.</p> <p>Methods</p> <p>Semi-structured, in-depth interviews were conducted with 17 women. They were all 35 to 49 years old, regularly menstruating, sexually active, not sterilized, not desiring a pregnancy in the near future, and at least 3 months postpartum. We purposely sampled for women who had had at least one unintended pregnancy after age 35 (n = 9) and women who did not (n = 8). We assessed partnership, views of pregnancy and motherhood, desired lifestyle, perceived advantages and disadvantages of using and obtaining currently available well-known reversible contraceptives in the U.S. ''We also assessed contraceptive methods used at any time during their reproductive years, including current method use and, if appropriate, circumstances surrounding an unintended pregnancy after age 35.'' Each interview was taped and transcribed verbatim. Data were analyzed using Grounded Theory. Analysis focused on partnership, views of pregnancy, motherhood, desired lifestyle and perceived advantages and disadvantages of various reversible contraceptive methods.</p> <p>Results</p> <p>The women without an unintended pregnancy after age 35 were more likely to (1) use contraceptive methods that helped treat a medical condition, (2) consider pregnancy as dangerous, or (3) express concerns about the responsibilities of motherhood. The women who experienced an unintended pregnancy after age 35 were more likely to (1) report unstable partnerships, (2) perceive themselves at lower risk of pregnancy, or (3) report past experiences with unwanted contraceptive side effects. There was a greater likelihood a woman would choose a contraceptive method if it was perceived as easy to use, accessible, affordable and had minimal side effects.</p> <p>Conclusions</p> <p>Women's perspective on contraceptive use after age 35 varies. Public health messages and health providers' care can help women in this age group by reviewing their fertility risks, as well as all contraceptive methods and their associated side effects. The impact of such interventions on unintended pregnancy rates in this age group should be tested in other areas of evidence-based medicine.</p