Validation of a French language version of the Early Childhood Oral Health Impact Scale (ECOHIS)

© 2008 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Small Intensely Fluorescent Cells in Culture: Role of Glucocorticoids and Growth Factors in Their Development and lnterconversions with other Neural Crest Derivatives

The neural crest gives rise to a number of adrenergic derivatives, including sympathetic neurons and adrenal chromaffin cells, which contain catecholamines (CAs) but differ in other morphological and functional characteristics. Small intensely fluorescent (SIF) cells, which exist primarily as a minority cell population in autonomic ganglia, are a third cell type in the sympathoadrenal branch of the neural crest lineage. In some respects these cells appear intermediate in phenotype between sympathetic neurons and adrenal chromaffin cells. We established pure dissociated cell cultures of SIF cells from rat superior cervical ganglia (SCG) and used these to study the role of environmental factors in SIF cell development and the relationship of these cells to the other cell types of the sympathoadrenal lineage. When cells from neonatal rat SCG were grown for 3 weeks in the presence of glucocorticoid and in the absence of nerve growth factor (NGF), pure cultures of SIF cells developed. The properties of the cells included (i) small cell size and the occasional presence of short neurites, (ii) intense CA histofluorescence and immunoreactivity for CA synthetic enzymes, (iii) synthesis and storage of CA from radioactive precursors, and (iv) characteristic ultrastructure. The concentration of the glucocorticoid and the presence or absence of non-neuronal cell factors influenced which types of SIF cells developed. In micromolar glucocorticoid most of the cells resembled adrenal chromaffin or type II SIF cells: they displayed immunohistochemically detectable phenylethanolamine-N-methyltransferase (PNMT), synthesized and stored epinephrine, and contained large granular vesicles (100 to 300 nm). When SCG cells were grown in 10(-8) M hormone, many fewer SIF cells developed and a higher percentage of these lacked PNMT immunoreactivity, had neurites, and contained vesicles of smaller mean diameter (70 to 130 nm), similar to those of type I SIF cells in vivo. In the presence of conditioned medium (medium conditioned by non- neuronal cells) as well as glucocorticoid, virtually all of the cells morphologically resembled type I SIF cells. In the absence of glucocorticoid, no SIF cells were ever observed after 3 weeks in culture. By following the development of CA histofluorescence and SIF cell ultrastructure in the cultures over time, we demonstrated that SIF cells were not present in large numbers in these cultures immediately after plating, but were induced from an apparently undifferentiated precursor by the hormonal environment, whereas most of the principal neurons died

The rapid emergence of stimulus specific perceptual learning

Is stimulus specific perceptual learning the result of extended practice or does it emerge early in the time course of learning? We examined this issue by manipulating the amount of practice given on a face identification task on Day 1, and altering the familiarity of stimuli on Day 2. We found that a small number of trials was sufficient to produce stimulus specific perceptual learning of faces: on Day 2, response accuracy decreased by the same amount for novel stimuli regardless of whether observers practiced 105 or 840 trials on Day 1. Current models of learning assume early procedural improvements followed by late stimulus specific gains. Our results show that stimulus specific and procedural improvements are distributed throughout the time course of learning

Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution

Cross-cultural adaptation of the Child Perceptions Questionnaire 11–14 (CPQ11–14) for the Brazilian Portuguese language

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Toward integrated conservation of North America's crop wild relatives

North America harbors a rich native flora of crop wild relatives—the progenitors and closely related species of domesticated plants—as well as a range of culturally significant wild utilized plants. Despite their current and potential future value, they are rarely prioritized for conservation efforts; thus many species are threatened in their natural habitats, and most are underrepresented in plant genebanks and botanical gardens. Further coordination of efforts among land management, botanical, and agricultural science organizations will improve conservation and general public awareness with regard to these species. We present examples of productive collaborations focused on wild cranberries (Vaccinium macrocarpon and Vaccinium oxycoccos) and chile peppers (Capsicum annuum var. glabriusculum). We then discuss five shared priorities for further action: (1) understand and document North America's crop wild relatives and wild utilized plants, (2) protect threatened species in their natural habitats, (3) collect and conserve ex situ the diversity of prioritized species, (4) make this diversity accessible and attractive for plant breeding, research, and education, and (5) raise public awareness of their value and the threats to their persistence

Required Sample Size to Detect Mediation in 3-Level Implementation Studies

Background: Statistical tests of mediation are important for advancing implementation science; however, little research has examined the sample sizes needed to detect mediation in 3-level designs (e.g., organization, provider, patient) that are common in implementation research. Using a generalizable Monte Carlo simulation method, this paper examines the sample sizes required to detect mediation in 3-level designs under a range of conditions plausible for implementation studies. Method: Statistical power was estimated for 17,496 3-level mediation designs in which the independent variable (X) resided at the highest cluster level (e.g., organization), the mediator (M) resided at the intermediate nested level (e.g., provider), and the outcome (Y) resided at the lowest nested level (e.g., patient). Designs varied by sample size per level, intraclass correlation coefficients of M and Y, effect sizes of the two paths constituting the indirect (mediation) effect (i.e., X→M and M→Y), and size of the direct effect. Power estimates were generated for all designs using two statistical models—conventional linear multilevel modeling of manifest variables (MVM) and multilevel structural equation modeling (MSEM)—for both 1- and 2-sided hypothesis tests. Results: For 2-sided tests, statistical power to detect mediation was sufficient (≥0.8) in only 463 designs (2.6%) estimated using MVM and 228 designs (1.3%) estimated using MSEM; the minimum number of highest-level units needed to achieve adequate power was 40; the minimum total sample size was 900 observations. For 1-sided tests, 808 designs (4.6%) estimated using MVM and 369 designs (2.1%) estimated using MSEM had adequate power; the minimum number of highest-level units was 20; the minimum total sample was 600. At least one large effect size for either the X→M or M→Y path was necessary to achieve adequate power across all conditions. Conclusions: While our analysis has important limitations, results suggest many of the 3-level mediation designs that can realistically be conducted in implementation research lack statistical power to detect mediation of highest-level independent variables unless effect sizes are large and 40 or more highest-level units are enrolled. We suggest strategies to increase statistical power for multilevel mediation designs and innovations to improve the feasibility of mediation tests in implementation research

Rotamer-Restricted Fluorogenicity Of The Bis-Arsenical ReAsH

Fluorogenic dyes such as FlAsH and ReAsH are used widely to localize, monitor, and characterize proteins and their assemblies in live cells. These bis-arsenical dyes can become fluorescent when bound to a protein containing four proximal Cys thiols—a tetracysteine (Cys4) motif. Yet the mechanism by which bis-arsenicals become fluorescent upon binding a Cys4 motif is unknown, and this nescience limits more widespread application of this tool. Here we probe the origins of ReAsH fluorogenicity using both computation and experiment. Our results support a model in which ReAsH fluorescence depends on the relative orientation of the aryl chromophore and the appended arsenic chelate: the fluorescence is rotamer-restricted. Our results do not support a model in which fluorogenicity arises from the relief of ring strain. The calculations identify those As–aryl rotamers that support fluorescence and those that do not and correlate well with prior experiments. The rotamer-restricted model we propose is supported further by biophysical studies: the excited-state fluorescence lifetime of a complex between ReAsH and a protein bearing a high-affinity Cys4 motif is longer than that of ReAsH-EDT2, and the fluorescence intensity of ReAsH-EDT2 increases in solvents of increasing viscosity. By providing a higher resolution view of the structural basis for fluorogenicity, these results provide a clear strategy for the design of more selective bis-arsenicals and better-optimized protein targets, with a concomitant improvement in the ability to characterize previously invisible protein conformational changes and assemblies in live cells

The Learning Curve in Percutaneous Repair of Paravalvular Prosthetic Regurgitation An Analysis of 200 Cases

ObjectivesThis study sought to assess the learning curve for percutaneous repair of paravalvular prosthetic regurgitation.BackgroundPercutaneous repair of prosthetic paravalvular regurgitation is a complex procedure. There is a paucity of data on the professional experience and tools needed to achieve optimal clinical outcomes.MethodsWe examined the chronological experience of 200 patients (age 66 ± 13 years; 57% men) who underwent percutaneous closure of paravalvular prosthetic regurgitation at our institution. A sequence number of the patient was assigned as a continuous variable for analysis.ResultsA total of 243 paravalvular defects (74% mitral; 26% aortic) were treated. Device delivery was successful in 92% with an average procedural time of 139 ± 47 min. The 30-day rate of major adverse cardiovascular events was 7%. With increased case experience and adoption of dedicated imaging and catheter techniques, there were decreases in procedural time, fluoroscopy time, contrast volume administered, length of hospital stay, and major adverse cardiovascular events. Procedural success remained unchanged throughout the experience. The predominant reason for procedural failure was prosthetic leaflet impingement, which accounted for 9 of 21 failed cases.ConclusionsIn this single-center experience, there was evidence of a learning curve that occurred with the adoption of dedicated techniques for catheter delivery and echocardiographic imaging. In experienced operators, the potential for prosthetic leaflet impingement is the predominant limitation of the procedure. These data have implications for physician training and performance in complex structural heart disease interventions

Simulated LSST Survey of RR Lyrae Stars throughout the Local Group

We report on a study to determine the efficiency of the Large Synoptic Survey Telescope (LSST) to recover the periods, brightnesses, and shapes of RR Lyrae stars' light curves in the volume extending to heliocentric distances of 1.5 Mpc. We place the smoothed light curves of 30 type ab and 10 type c RR Lyrae stars in 1007 fields across the sky, each of which represents a different realization of the LSST sampling cadences, and that sample five particular observing modes. A light curve simulation tool was used to sample the idealized RR Lyrae stars' light curves, returning each as it would have been observed by LSST, including realistic photometric scatter, limiting magnitudes, and telescope downtime. We report here the period, brightness, and light curve shape recovery as a function of apparent magnitude and for survey lengths varying from 1 to 10 years. We find that 10 years of LSST data are sufficient to recover the pulsation periods with a fractional precision of ~10^(–5) for ≥90% of ab stars within ≈360 kpc of the Sun in Universal Cadence fields and out to ≈760 kpc for Deep Drilling fields. The 50% completeness level extends to ≈600 kpc and ≈1.0 Mpc for the same fields, respectively. For virtually all stars that had their periods recovered, their light curve shape parameter φ_31 was recovered with sufficient precision to also recover photometric metallicities to within 0.14 dex (the systematic error in the photometric relations). With RR Lyrae stars' periods and metallicities well measured to these distances, LSST will be able to search for halo streams and dwarf satellite galaxies over half of the Local Group, informing galaxy formation models and providing essential data for mapping the Galactic potential. This study also informs the LSST science operations plan for optimizing observing strategies to achieve particular science goals. We additionally present a new [Fe/H]-φ_31 photometric relation in the r band and a new and generally useful metric for defining period recovery for time domain surveys