THE EVALUATION OF PAIN EXPERIENCED BY CHILDREN UNDERGOING SIMPLE EXTRACTION USING 2% LIDOCAINE VERSUS ORAQIX TOPICAL ANESTHETIC GEL

Purpose: The purpose of this study is to examine the pain response experienced by children undergoing simple tooth extractions using 2% Lidocaine injection versus Oraqix topical anesthetic gel. Methods: This study is being conducted at VCU pediatric dentistry clinic. The sample size will consist of 15 children ages 7-12 undergoing a simple extraction procedure. Each participant is randomly assigned to one of two groups, the lidocaine injection group or the Oraqix topical group. The pain level will be measured at four key events during the procedure. The first event will evaluate the pain at baseline. The second event will measure pain during the anesthetic injection or Oraqix topical gel application. The third event will record the response after the tooth has been extracted and the final event will evaluate pain five minutes post operatively. The children are asked to rate their pain using the Facial Pain Scale after all four events. The dentist and an independent observer watching a video of the extraction will also examine and rate the pain responses of each child at each of the four events. Results: The first two participants received lidocaine injection and experienced some pain upon injection. This pain was supported by what the dentist rated as well. One child felt pain on extraction and the other felt nothing. The dentist rated both children as feeling pain. The Oraqix child felt nothing upon application but felt pain during the extraction and post-operatively. The dentist rated the child as feeling nothing during the entire procedure. Conclusions: It appears that the lidocaine injection group’s pain rating matches the pain rating given by the dentist. The Oraqix patient experienced no pain upon application, but did feel pain upon extraction and five minutes post-op. The dentist’s rating contradicted this by rating the child as feeling no pain through the entire procedure. This study is limited by the number of participants and needs more patients to further evaluate other children’s pain responses

A Conformation Change in the Extracellular Domain that Accompanies Desensitization of Acid-sensing Ion Channel (ASIC) 3

Acid-sensing ion channels (ASICs) are thought to trigger some forms of acid-induced pain and taste, and to contribute to stroke-induced neural damage. After activation by low extracellular pH, different ASICs undergo desensitization on time scales from 0.1 to 10 s. Consistent with a substantial conformation change, desensitization slows dramatically when temperature drops (Askwith, C.C., C.J. Benson, M.J. Welsh, and P.M. Snyder. 2001. PNAS. 98:6459–6463). The nature of this conformation change is unknown, but two studies showed that desensitization rate is altered by mutations on or near the first transmembrane domain (TM1) (Coric, T., P. Zhang, N. Todorovic, and C.M. Canessa. 2003. J. Biol. Chem. 278:45240–45247; Pfister, Y., I. Gautschi, A.-N. Takeda, M. van Bemmelen, S. Kellenberger, and L. Schild. 2006. J. Biol. Chem. 281:11787–11791). Here we show evidence of a specific conformation change associated with desensitization. When mutated from glutamate to cysteine, residue 79, which is some 20 amino acids extracellular to TM1, can be altered by cysteine-modifying reagents when the channel is closed, but not when it is desensitized; thus, desensitization appears to conceal the residue from the extracellular medium. D78 and E79 are a pair of adjacent acidic amino acids that are highly conserved in ASICs yet absent from epithelial Na+ channels, their acid-insensitive relatives. Despite large effects on desensitization by mutations at positions 78 and 79—including a shift to 10-fold lower proton concentration with the E79A mutant—there are not significant effects on activation

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. Setting Multinational study of 9306 participants. Participants: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. Outcome measures: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. Results: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ2=16.8; p<0.0001), but not change in weight (χ2=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ2=5.9; p=0.02) but not previous step count (χ2=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ2 for previous weight measurements 747.3; p<0.0001) and physical activity (χ2 for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. Conclusions: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables

Estimating the Porosity of the Interstellar Medium from Three-Dimensional Photoionization Modeling of H II Regions

We apply our three dimensional photoionization code to model Wisconsin H-alpha Mapper observations of the H II region surrounding the O9.5V star Zeta Oph. Our models investigate the porosity of the interstellar medium around zeta Oph and the effects of 3D densities on the H-alpha surface brightness and variation in the [N II]/H-alpha line ratio. The Zeta Oph H II region has a well characterized ionizing source, so it is an excellent starting point for 3D models of diffuse ionized gas. We investigate various hierarchically clumped density structures, varying the overall smoothness within the clumping algorithm. By simulating the observations, we can estimate the porosity of the medium in the vicinity of Zeta Oph and find that within the context of our hierarchically clumped models, around 50% to 80% of the volume is occupied by clumps surrounded by a low density smooth medium. We also conclude that in order for O stars to ionize the diffuse Warm Ionized Medium, the O star environment must be more porous than that surrounding Zeta Oph, with clumps occupying less than one half of the interstellar volume. Our clumpy models have irregular boundaries, similar to observed H II regions. However, in observed H II regions it is difficult to identify the precise location of the boundary because of the foreground and/or background emission from the widespread Warm Ionized Medium. This complicates the interpretation of the predicted rapid rise of some emission line ratios near the edge of uniform density H II regions and combined with the three dimensional clumpy nature of the interstellar medium may explain the apparent lack of distinctive emission line ratios near H I -- H II interfaces.Comment: Accepted for publication in Ap

N-terminal pro-B-type natriuretic peptide by itself predicts death and cardiovascular events in high-risk patients with type 2 diabetes

Background: NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) improves the discriminatory ability of risk‐prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT‐proBNP by itself for death and cardiovascular events in high‐risk patients with T2DM. Methods and Results: Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT‐proBNP alone and with NT‐proBNP added, using C‐statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6‐year follow‐up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT‐proBNP alone was as discriminatory as the base model for predicting death (C‐statistic, 0.745 versus 0.744, P=0.95) and the cardiovascular composite outcome (C‐statistic, 0.723 versus 0.731, P=0.37). When NT‐proBNP was added, it increased the predictive ability of the base model for death (C‐statistic, 0.779 versus 0.744, P<0.001) and for cardiovascular composite outcome (C‐statistic, 0.763 versus 0.731, P<0.001). Conclusions: In high‐risk patients with T2DM, NT‐proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification

Monte Carlo Photoionization Simulations of Diffuse Ionized Gas

We demonstrate that the observed increase of some nebular line ratios with height above the midplane in the diffuse ionized gas (DIG) in the Milky Way and other galaxies is a natural consequence of the progressive hardening of the radiation field far from the midplane ionizing sources. To obtain increasing temperatures and line ratios away from the midplane, our photoionization simulations of a multi-component interstellar medium do not require as much additional heating (over and above that from photoionization) as previous studies that employed one dimensional, spherically averaged models. Radiation leaking into the DIG from density bounded H II regions is generally harder in the H-ionizing continuum and has its He-ionizing photons suppressed compared to the ionizing source of the H II region. In line with other recent investigations, we find that such leaky H II region models can provide elevated temperatures and line ratios, and a lower He+ fraction in the DIG. For a composite model representing the relative spectral types of O stars in the solar neighbourhood, we find that additional heating less than 1.0E-26 n_e ergs/s/cm^3 can reproduce the observed elevated line ratios in the DIG. This additional heating is considerably less than previous estimates due to the natural hardening of the radiation field reaching large heights in our simulations.Comment: Accepted for publication in MNRA

Overweight, physical activity, tobacco and alcohol consumption in a cross-sectional random sample of German adults

BACKGROUND: There is a current paucity of data on the health behaviour of non-selected populations in Central Europe. Data on health behaviour were collected as part of the EMIL study which investigated the prevalence of infection with Echinococcus multilocularis and other medical conditions in an urban German population. METHODS: Participating in the present study were 2,187 adults (1,138 females [52.0%]; 1,049 males [48.0%], age: 18–65 years) taken from a sample of 4,000 persons randomly chosen from an urban population. Data on health behaviour like physical activity, tobacco and alcohol consumption were obtained by means of a questionnaire, documentation of anthropometric data, abdominal ultrasound and blood specimens for assessment of chemical parameters. RESULTS: The overall rate of participation was 62.8%. Of these, 50.3% of the adults were overweight or obese. The proportion of active tobacco smokers stood at 30.1%. Of those surveyed 38.9% did not participate in any physical activity. Less than 2 hours of leisure time physical activity per week was associated with female sex, higher BMI (Body Mass Index), smoking and no alcohol consumption. Participants consumed on average 12 grams of alcohol per day. Total cholesterol was in 62.0% (>5.2 mmol/l) and triglycerides were elevated in 20.5% (≥ 2.3 mmol/l) of subjects studied. Hepatic steatosis was identified in 27.4% of subjects and showed an association with male sex, higher BMI, higher age, higher total blood cholesterol, lower HDL, higher triglycerides and higher ALT. CONCLUSION: This random sample of German urban adults was characterised by a high prevalence of overweight and obesity. This and the pattern of alcohol consumption, smoking and physical activity can be considered to put this group at high risk for associated morbidity and underscore the urgent need for preventive measures aimed at reducing the significantly increased health risk