Randomized Controlled Trial of Postoperative Sensitivity with Warm and Room Temperature Composite

Physical properties of composite improve when it is preheated prior to polymerization. However, postoperative sensitivity may be considered a potential complication. A review of the literature revealed no reported randomized controlled trials (RCTs) of postoperative sensitivity when using preheated composite resin. The objective of the study was to determine if preheating composite leads to changes in postoperative sensitivity in a parallel RCT. In total, 120 eligible, consenting adults were recruited in private dental practice and randomized into 2 groups of 60 patients. One group had room temperature composite restorations placed and the second had composite preheated to 39°C. The primary outcome was sensitivity after 24 h by the visual analog scale (VAS), recorded blind by patients. Secondary outcomes were VAS scores recorded over a month. Blind statistical analysis used the Mann-Whitney U test to compare the 24-h VAS score between groups and repeated-measures analysis of variance to assess the change over time. Potential confounders were tested using regression models. A total of 115 patients completed the trial: 57 in the heated composite group and 58 in the room temperature group. Analysis of 24-h VAS scores found no statistically significant difference between the 2 groups (P = 0.162). Examining the potential confounders confirmed the nonsignificant difference between heated and room temperature groups on the 24-h VAS score, after controlling teeth type and preoperative pulp test (effect size = 0.173, P = 0.317). Analysis of the secondary outcomes found significant changes (within-subject effect) in VAS scores over the review period (F statistic = 4.7, P = 0.002) but not a significant (between-subject effect) difference between heated and room temperature groups over time (effect size = 0.102, P = 0.197). There was a significant correlation between preoperative VAS score and postoperative VAS score (P < 0.001). For the restorations in this study, there was no detectable difference in postoperative VAS score between preheated and room temperature composite. Postoperative sensitivity decreased throughout the first month. Postoperative sensitivity was correlated to preoperative sensitivity (ISRCTN 76727312). Knowledge Transfer Statement: The results of this study can be used by clinicians when considering the advantages and disadvantages of preheated composite. The study found no evidence of any change in postoperative sensitivity when using preheated composite. Since preheated composite has superior physical properties, its use for routine care can be considered good practice

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

Improvdent: Improving dentures for patient benefit. A crossover randomised clinical trial comparing impression materials for complete dentures.

Background According to the UK Adult Dental Health Survey (2009) 15% of adults aged 65–74, 30% aged 75–84 and 47% aged >85 years are edentulous and require complete dentures. Patients’ quality of life and nutrition status are affected by poor dentures. The quality of the dental impression is the most important issue for improving the fit and comfort of new dentures. There is paucity of RCT evidence for which impression material is best for complete dentures construction. This study aims to compare two impression materials for effectiveness and cost effectiveness. Methods/Design IMPROVDENT is a double-blind crossover trial comparing the use of alginate and silicone, two commonly used denture impression materials, in terms of patient preference and cost-effectiveness. Eighty five edentulous patients will be recruited and provided with two sets of dentures, similar in all aspects except for the impression material used (alginate or silicone). Patients will try both sets of dentures for a two-week period, unadjusted, to become accustomed to the feel of the new dentures (habituation period). Patients will then wear each set of dentures for a period of 8 weeks (in random order) during which time the dentures will be adjusted for optimum comfort. Finally, patients will be given both sets of dentures for a further two weeks to wear whichever denture they prefer (confirmation period). Patients will be asked about quality of life and to rate dentures on function and comfort at the end of each trial period and asked which set they prefer at the end of the habituation period (unadjusted denture preference) and confirmation period (adjusted denture preference). A health economic evaluation will estimate incremental cost-effectiveness ratios of producing dentures from the two materials. A qualitative study will investigate the impact of dentures on behaviour and quality of life. Funding: IMPROVDENT is funded by NIHR RfPB (PB-PG-0408-16300). Discussion This trial aims to provide evidence on the costs and quality of dentures cast from two different commonly used impression materials; the intention is to significantly impact on the quality of denture production within NHS dentistry

A Mild Form of SLC29A3 Disorder: A Frameshift Deletion Leads to the Paradoxical Translation of an Otherwise Noncoding mRNA Splice Variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the ‘rescue’ role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic

Does the gender of the subject affect perceived smile aesthetics when varying the dimensions of maxillary lateral incisors?

Objective To assess whether subject gender influences aesthetic opinion when altering the width of maxillary lateral incisors. Method Photographs of a male and a female smile, displaying only the lips and teeth, were digitally altered to produce images where the maxillary lateral incisor was proportioned 52%, 57%, 62%, 67%, 72% and 77% in relation to the width of the maxillary central incisor. The image was then made symmetrical. One hundred participants (50 male and 50 female) were asked to rank each set of photographs from 'most' to 'least attractive'. Result The 57% lateral incisor was considered the 'most attractive' with the 77% lateral incisor the 'least attractive' however no statistically significant difference existed with relation to subject or rater gender. Conclusion Neither the 'golden proportion' nor the 'Recurrent Aesthetic Dental' ('RED') proportion was deemed the most attractive. As subject gender did not have a significant effect, dentists should work to create aesthetic results on an individual basis, operating within a so-called 'golden range'

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

The genomics of heart failure: design and rationale of the HERMES consortium

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01–0.05) at P < 5 × 10^{-8} under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta