Efficacy of a Dissolvable Strip with Calcium Sodium Phosphosilicate (NovaMin®) in Providing Rapid Dentine Hypersensitivity Relief

Objective To evaluate the efficacy of a dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) (Novamin®) in providing rapid relief from dentine hypersensitivity (DH). Methods In this examiner-blind, proof-of-principle study, 120 healthy adults with DH were randomized 1:1 to the Test strip, professionally applied to facial surfaces of two selected teeth, or to No treatment. Sensitivity was assessed at baseline and 10 min, 2 h and 4 h post-application in response to evaporative (air) and tactile stimuli (measured by Schiff sensitivity scale/a numeric rating scale and tactile threshold, respectively). Change from baseline was analyzed by ANCOVA. Results At 10 min post-application, mean Schiff score change from baseline (primary endpoint) was statistically significant with the Test strip (−0.46; 95% confidence intervals [CI]: −0.563, −0.356; p \u3c 0.0001) but not with No treatment (−0.02; 95% CI: −0.119, 0.088; p = 0.7664). The between-treatment group difference favored the Test strip (difference: −0.44; 95% CI: −0.591, −0.297; p \u3c 0.0001). Similar improvements with the Test strip were reported for all other evaporative (air) and tactile sensitivity endpoints (p \u3c 0.0001 vs no-treatment) at all timepoints (10 min, 2 h, 4 h). Test strips were considered by most staff and participants slightly/moderately easy to apply (98%). Many participants rated the overall usage experience as “like moderately” (40%) or “like extremely” (20%). There were no treatment-related adverse events. Conclusion This new CSPS-based technology may provide a novel treatment option for rapid relief from DH (Clinicaltrials.gov NCT02937623). Clinical significance A dissolvable strip containing 15% w/w calcium sodium phosphosilicate (CSPS) demonstrated significantly greater dentine hypersensitivity reductions following a single application compared with no treatment. Strips were well-liked by participants and generally well tolerated. A strip containing CSPS, which dissolves within 10 min, may provide rapid relief from dentine hypersensitivity

Application of a rank-based genetic association test to age-at-onset data from the Collaborative Study on the Genetics of Alcoholism study

Association studies of quantitative traits have often relied on methods in which a normal distribution of the trait is assumed. However, quantitative phenotypes from complex human diseases are often censored, highly skewed, or contaminated with outlying values. We recently developed a rank-based association method that takes into account censoring and makes no distributional assumptions about the trait. In this study, we applied our new method to age-at-onset data on ALDX1 and ALDX2. Both traits are highly skewed (skewness > 1.9) and often censored. We performed a whole genome association study of age at onset of the ALDX1 trait using Illumina single-nucleotide polymorphisms. Only slightly more than 5% of markers were significant. However, we identified two regions on chromosomes 14 and 15, which each have at least four significant markers clustering together. These two regions may harbor genes that regulate age at onset of ALDX1 and ALDX2. Future fine mapping of these two regions with densely spaced markers is warranted

Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Inhomogeneous Magnetism in La-doped CaMnO3. (II) Mesoscopic Phase Separation due to Lattice-coupled FM Interactions

A detailed investigation of mesoscopic magnetic and crystallographic phase separation in Ca(1-x)La(x)MnO3, 0.00<=x<=0.20, is reported. Neutron powder diffraction and DC-magnetization techniques have been used to isolate the different roles played by electrons doped into the eg level as a function of their concentration x. The presence of multiple low-temperature magnetic and crystallographic phases within individual polycrystalline samples is argued to be an intrinsic feature of the system that follows from the shifting balance between competing FM and AFM interactions as a function of temperature. FM double-exchange interactions associated with doped eg electrons are favored over competing AFM interactions at higher temperatures, and couple more strongly with the lattice via orbital polarization. These FM interactions thereby play a privileged role, even at low eg electron concentrations, by virtue of structural modifications induced above the AFM transition temperatures.Comment: 8 pages, 7 figure

Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Membranes for Topological M-Theory

We formulate a theory of topological membranes on manifolds with G_2 holonomy. The BRST charges of the theories are the superspace Killing vectors (the generators of global supersymmetry) on the background with reduced holonomy G_2. In the absence of spinning formulations of supermembranes, the starting point is an N=2 target space supersymmetric membrane in seven euclidean dimensions. The reduction of the holonomy group implies a twisting of the rotations in the tangent bundle of the branes with ``R-symmetry'' rotations in the normal bundle, in contrast to the ordinary spinning formulation of topological strings, where twisting is performed with internal U(1) currents of the N=(2,2) superconformal algebra. The double dimensional reduction on a circle of the topological membrane gives the strings of the topological A-model (a by-product of this reduction is a Green-Schwarz formulation of topological strings). We conclude that the action is BRST-exact modulo topological terms and fermionic equations of motion. We discuss the role of topological membranes in topological M-theory and the relation of our work to recent work by Hitchin and by Dijkgraaf et al.Comment: 22 pp, plain tex. v2: refs. adde

Diagnosis of childhood tuberculosis and host RNA expression in Africa

Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV

Health services research in the public healthcare system in Hong Kong: An analysis of over 1 million antihypertensive prescriptions between 2004-2007 as an example of the potential and pitfalls of using routinely collected electronic patient data

&lt;b&gt;Objectives&lt;/b&gt; Increasing use is being made of routinely collected electronic patient data in health services research. The aim of the present study was to evaluate the potential usefulness of a comprehensive database used routinely in the public healthcare system in Hong Kong, using antihypertensive drug prescriptions in primary care as an example.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Data on antihypertensive drug prescriptions were retrieved from the electronic Clinical Management System (e-CMS) of all primary care clinics run by the Health Authority (HA) in the New Territory East (NTE) cluster of Hong Kong between January 2004 and June 2007. Information was also retrieved on patients’ demographic and socioeconomic characteristics, visit type (new or follow-up), and relevant diseases (International Classification of Primary Care, ICPC codes). &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; 1,096,282 visit episodes were accessed, representing 93,450 patients. Patients’ demographic and socio-economic details were recorded in all cases. Prescription details for anti-hypertensive drugs were missing in only 18 patients (0.02%). However, ICPC-code was missing for 36,409 patients (39%). Significant independent predictors of whether disease codes were applied included patient age &gt; 70 years (OR 2.18), female gender (OR 1.20), district of residence (range of ORs in more rural districts; 0.32-0.41), type of clinic (OR in Family Medicine Specialist Clinics; 1.45) and type of visit (OR follow-up visit; 2.39). &lt;p&gt;&lt;/p&gt; In the 57,041 patients with an ICPC-code, uncomplicated hypertension (ICPC K86) was recorded in 45,859 patients (82.1%). The characteristics of these patients were very similar to those of the non-coded group, suggesting that most non-coded patients on antihypertensive drugs are likely to have uncomplicated hypertension. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; The e-CMS database of the HA in Hong Kong varies in quality in terms of recorded information. Potential future health services research using demographic and prescription information is highly feasible but for disease-specific research dependant on ICPC codes some caution is warranted. In the case of uncomplicated hypertension, future research on pharmaco-epidemiology (such as prescription patterns) and clinical issues (such as side-effects of medications on metabolic parameters) seems feasible given the large size of the data set and the comparability of coded and non-coded patients

Deep Sequencing of Small RNAs in Tomato for Virus and Viroid Identification and Strain Differentiation

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals

Use of weekly, low dose, high frequency ultrasound for hard to heal venous leg ulcers: the VenUS III randomised controlled trial

Objective To assess the clinical effectiveness of weekly delivery of low dose, high frequency therapeutic ultrasound in conjunction with standard care for hard to heal venous leg ulcers