The complete digital workflow in fixed prosthodontics: a systematic review

Background The continuous development in dental processing ensures new opportunities in the field of fixed prosthodontics in a complete virtual environment without any physical model situations. The aim was to compare fully digitalized workflows to conventional and/or mixed analog-digital workflows for the treatment with tooth-borne or implant-supported fixed reconstructions. Methods A PICO strategy was executed using an electronic (MEDLINE, EMBASE, Google Scholar) plus manual search up to 2016–09-16 focusing on RCTs investigating complete digital workflows in fixed prosthodontics with regard to economics or esthetics or patient-centered outcomes with or without follow-up or survival/success rate analysis as well as complication assessment of at least 1 year under function. The search strategy was assembled from MeSH-Terms and unspecific free-text words: {((“Dental Prosthesis” [MeSH]) OR (“Crowns” [MeSH]) OR (“Dental Prosthesis, Implant-Supported” [MeSH])) OR ((crown) OR (fixed dental prosthesis) OR (fixed reconstruction) OR (dental bridge) OR (implant crown) OR (implant prosthesis) OR (implant restoration) OR (implant reconstruction))} AND {(“Computer-Aided Design” [MeSH]) OR ((digital workflow) OR (digital technology) OR (computerized dentistry) OR (intraoral scan) OR (digital impression) OR (scanbody) OR (virtual design) OR (digital design) OR (cad/cam) OR (rapid prototyping) OR (monolithic) OR (full-contour))} AND {(“Dental Technology” [MeSH) OR ((conventional workflow) OR (lost-wax-technique) OR (porcelain-fused-to-metal) OR (PFM) OR (implant impression) OR (hand-layering) OR (veneering) OR (framework))} AND {((“Study, Feasibility” [MeSH]) OR (“Survival” [MeSH]) OR (“Success” [MeSH]) OR (“Economics” [MeSH]) OR (“Costs, Cost Analysis” [MeSH]) OR (“Esthetics, Dental” [MeSH]) OR (“Patient Satisfaction” [MeSH])) OR ((feasibility) OR (efficiency) OR (patient-centered outcome))}. Assessment of risk of bias in selected studies was done at a ‘trial level’ including random sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other bias using the Cochrane Collaboration tool. A judgment of risk of bias was assigned if one or more key domains had a high or unclear risk of bias. An official registration of the systematic review was not performed. Results The systematic search identified 67 titles, 32 abstracts thereof were screened, and subsequently, three full-texts included for data extraction. Analysed RCTs were heterogeneous without follow-up. One study demonstrated that fully digitally produced dental crowns revealed the feasibility of the process itself; however, the marginal precision was lower for lithium disilicate (LS2) restorations (113.8 μm) compared to conventional metal-ceramic (92.4 μm) and zirconium dioxide (ZrO2) crowns (68.5 μm) (p < 0.05). Another study showed that leucite-reinforced glass ceramic crowns were esthetically favoured by the patients (8/2 crowns) and clinicians (7/3 crowns) (p < 0.05). The third study investigated implant crowns. The complete digital workflow was more than twofold faster (75.3 min) in comparison to the mixed analog-digital workflow (156.6 min) (p < 0.05). No RCTs could be found investigating multi-unit fixed dental prostheses (FDP). Conclusions The number of RCTs testing complete digital workflows in fixed prosthodontics is low. Scientifically proven recommendations for clinical routine cannot be given at this time. Research with high-quality trials seems to be slower than the industrial progress of available digital applications. Future research with well-designed RCTs including follow-up observation is compellingly necessary in the field of complete digital processing

Psoriatic Arthritis and Burden of Disease: Patient Perspectives from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey

Introduction: Psoriatic arthritis (PsA) is underdiagnosed and has a substantial impact on quality of life, disability, and work productivity. The population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey examined the impact of PsA on patients’ activities of daily living and unmet treatment needs. Methods: This large-scale, random digit dialing, telephone survey of patients self-reporting a diagnosis of psoriasis and/or PsA was conducted in North America and Europe. Results: In all, 3426 patients participated in the survey, including 712 (21%) who identified themselves as having PsA. Over half of the patients reported severe PsA involving more than four joints. Eighty-three percent of patients with PsA visited a health-care provider within the past 12 months. Approximately one-quarter saw their primary care provider or dermatologist most often for their disease; 37% responded that their rheumatologist was the health-care provider seen most often for PsA. Patients with PsA reported a substantial impact of disease on physical function. One-third of patients with PsA reported missing work because of their disease and PsA impacted their ability to work full time. Over half of the patients with PsA (58%) reported receiving no treatment or topical therapy only, leaving their joint disease untreated. Factors associated with lack of adherence were perceived lack of efficacy and concerns about long-term safety. Conclusions: The MAPP survey confirms that PsA has a significant impact on physical function and activities of daily living. Undertreatment of PsA suggests a need for improved screening and diagnosis as well as education about treatment options and adherence

Power-Law Inter-Spike Interval Distributions Infer a Conditional Maximization of Entropy in Cortical Neurons

The brain is considered to use a relatively small amount of energy for its efficient information processing. Under a severe restriction on the energy consumption, the maximization of mutual information (MMI), which is adequate for designing artificial processing machines, may not suit for the brain. The MMI attempts to send information as accurate as possible and this usually requires a sufficient energy supply for establishing clearly discretized communication bands. Here, we derive an alternative hypothesis for neural code from the neuronal activities recorded juxtacellularly in the sensorimotor cortex of behaving rats. Our hypothesis states that in vivo cortical neurons maximize the entropy of neuronal firing under two constraints, one limiting the energy consumption (as assumed previously) and one restricting the uncertainty in output spike sequences at given firing rate. Thus, the conditional maximization of firing-rate entropy (CMFE) solves a tradeoff between the energy cost and noise in neuronal response. In short, the CMFE sends a rich variety of information through broader communication bands (i.e., widely distributed firing rates) at the cost of accuracy. We demonstrate that the CMFE is reflected in the long-tailed, typically power law, distributions of inter-spike intervals obtained for the majority of recorded neurons. In other words, the power-law tails are more consistent with the CMFE rather than the MMI. Thus, we propose the mathematical principle by which cortical neurons may represent information about synaptic input into their output spike trains

Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies

The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different—omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed—omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and—omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure

A multilocus assay reveals high nucleotide diversity and limited differentiation among Scandinavian willow grouse (Lagopus lagopus)

<p>Abstract</p> <p>Background</p> <p>There is so far very little data on autosomal nucleotide diversity in birds, except for data from the domesticated chicken and some passerines species. Estimates of nucleotide diversity reported so far in birds have been high (~10^-3) and a likely explanation for this is the generally higher effective population sizes compared to mammals. In this study, the level of nucleotide diversity has been examined in the willow grouse, a non-domesticated bird species from the order Galliformes, which also holds the chicken. The willow grouse (<it>Lagopus lagopus</it>) has an almost circumpolar distribution but is absent from Greenland and the north Atlantic islands. It primarily inhabits tundra, forest edge habitats and sub-alpine vegetation. Willow grouse are hunted throughout its range, and regionally it is a game bird of great cultural and economical importance.</p> <p>Results</p> <p>We sequenced 18 autosomal protein coding loci from approximately 15–18 individuals per population. We found a total of 127 SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid replacement substitutions. Total nucleotide diversity (<it>π</it>_<it>t</it>) was between 1.30 × 10^-4and 7.66 × 10^-3(average <it>π</it>_{<it>t </it>}= 2.72 × 10^-3± 2.06 × 10^-3) and silent nucleotide diversity varied between 4.20 × 10^-4and 2.76 × 10^-2(average <it>π</it>_{<it>S </it>}= 9.22 × 10^-3± 7.43 × 10^-4). The synonymous diversity is approximately 20 times higher than in humans and two times higher than in chicken. Non-synonymous diversity was on average 18 times lower than the synonymous diversity and varied between 0 and 4.90 × 10^-3(average <it>π</it>_{<it>a </it>}= 5.08 × 10^-4± 7.43 × 10³), which suggest that purifying selection is strong in these genes. <it>F</it>_STvalues based on synonymous SNP's varied between -5.60 × 10^-4and 0.20 among loci and revealed low levels of differentiation among the four localities, with an overall value of <it>F</it>_ST= 0.03 (95% CI: 0.006 – 0.057) over 60 unlinked loci. Non-synonymous SNP's gave similar results. Low levels of linkage disequilibrium were observed within genes, with an average r²= 0.084 ± 0.110, which is expected for a large outbred population with no population differentiation. The mean per site per generation recombination parameter (ρ) was comparably high (0.028 ± 0.018), indicating high recombination rates in these genes.</p> <p>Conclusion</p> <p>We found unusually high levels of nucleotide diversity in the Scandinavian willow grouse as well as very little population structure among localities with up to 1647 km distance. There are also low levels of linkage disequilibrium within the genes and the population recombination rate is high, which is indicative of an old panmictic population, where recombination has had time to break up any haplotype blocks. The non-synonymous nucleotide diversity is low compared with the silent, which is in agreement with effective purifying selection, possibly due to the large effective population size.</p

Investigating the complex genetic architecture of ankle-brachial index, a measure of peripheral arterial disease, in non-Hispanic whites

<p>Abstract</p> <p>Background</p> <p>Atherosclerotic peripheral arterial disease (PAD) affects 8–10 million people in the United States and is associated with a marked impairment in quality of life and an increased risk of cardiovascular events. Noninvasive assessment of PAD is performed by measuring the ankle-brachial index (ABI). Complex traits, such as ABI, are influenced by a large array of genetic and environmental factors and their interactions. We attempted to characterize the genetic architecture of ABI by examining the main and interactive effects of individual single nucleotide polymorphisms (SNPs) and conventional risk factors.</p> <p>Methods</p> <p>We applied linear regression analysis to investigate the association of 435 SNPs in 112 positional and biological candidate genes with ABI and related physiological and biochemical traits in 1046 non-Hispanic white, hypertensive participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The main effects of each SNP, as well as SNP-covariate and SNP-SNP interactions, were assessed to investigate how they contribute to the inter-individual variation in ABI. Multivariable linear regression models were then used to assess the joint contributions of the top SNP associations and interactions to ABI after adjustment for covariates. We reduced the chance of false positives by 1) correcting for multiple testing using the false discovery rate, 2) internal replication, and 3) four-fold cross-validation.</p> <p>Results</p> <p>When the results from these three procedures were combined, only two SNP main effects in <it>NOS3</it>, three SNP-covariate interactions (<it>ADRB2 </it>Gly 16 – lipoprotein(a) and <it>SLC4A5 </it>– diabetes interactions), and 25 SNP-SNP interactions (involving SNPs from 29 different genes) were significant, replicated, and cross-validated. Combining the top SNPs, risk factors, and their interactions into a model explained nearly 18% of variation in ABI in the sample. SNPs in six genes (<it>ADD2, ATP6V1B1, PRKAR2B, SLC17A2, SLC22A3, and TGFB3</it>) were also influencing triglycerides, C-reactive protein, homocysteine, and lipoprotein(a) levels.</p> <p>Conclusion</p> <p>We found that candidate gene SNP main effects, SNP-covariate and SNP-SNP interactions contribute to the inter-individual variation in ABI, a marker of PAD. Our findings underscore the importance of conducting systematic investigations that consider context-dependent frameworks for developing a deeper understanding of the multidimensional genetic and environmental factors that contribute to complex diseases.</p

Adolescents, Adults and Rewards: Comparing Motivational Neurocircuitry Recruitment Using fMRI

Background: Adolescent risk-taking, including behaviors resulting in injury or death, has been attributed in part to maturational differences in mesolimbic incentive-motivational neurocircuitry, including ostensible oversensitivity of the nucleus accumbens (NAcc) to rewards. Methodology/Principal Findings: To test whether adolescents showed increased NAcc activation by cues for rewards, or by delivery of rewards, we scanned 24 adolescents (age 12–17) and 24 adults age (22–42) with functional magnetic resonance imaging while they performed a monetary incentive delay (MID) task. The MID task was configured to temporally disentangle potential reward or potential loss anticipation-related brain signal from reward or loss notification-related signal. Subjects saw cues signaling opportunities to win or avoid losing $0,$.50, or $5 for responding quickly to a subsequent target. Subjects then viewed feedback of their trial success after a variable interval from cue presentation of between 6 to17 s. Adolescents showed reduced NAcc recruitment by reward-predictive cues compared to adult controls in a linear contrast with non-incentive cues, and in a volume-of-interest analysis of signal change in the NAcc. In contrast, adolescents showed little difference in striatal and frontocortical responsiveness to reward deliveries compared to adults. Conclusions/Significance: In light of divergent developmental difference findings between neuroimaging incentive paradigms (as well as at different stages within the same task), these data suggest that maturational differences i

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14–8.23; P &lt; 0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19–3.77; P = 0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08–3.47; P = 0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10–5.50; P = 0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30–0.72; P=0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01– 1.04; P &lt; 0.001) and age (OR, 1.17; 95% CI, 1.08–1.26; P &lt; 0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54–0.69) and a specificity of 0.63 (95% CI, 0.59–0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study

Axonal Transmission in the Retina Introduces a Small Dispersion of Relative Timing in the Ganglion Cell Population Response

Background: Visual stimuli elicit action potentials in tens of different retinal ganglion cells. Each ganglion cell type responds with a different latency to a given stimulus, thus transforming the high-dimensional input into a temporal neural code. The timing of the first spikes between different retinal projection neurons cells may further change along axonal transmission. The purpose of this study is to investigate if intraretinal conduction velocity leads to a synchronization or dispersion of the population signal leaving the eye. Methodology/Principal Findings: We 'imaged' the initiation and transmission of light-evoked action potentials along individual axons in the rabbit retina at micron-scale resolution using a high-density multi-transistor array. We measured unimodal conduction velocity distributions (1.3 +/- 0.3 m/sec, mean +/- SD) for axonal populations at all retinal eccentricities with the exception of the central part that contains myelinated axons. The velocity variance within each piece of retina is caused by ganglion cell types that show narrower and slightly different average velocity tuning. Ganglion cells of the same type respond with similar latency to spatially homogenous stimuli and conduct with similar velocity. For ganglion cells of different type intraretinal conduction velocity and response latency to flashed stimuli are negatively correlated, indicating that differences in first spike timing increase (up to 10 msec). Similarly, the analysis of pair-wise correlated activity in response to white-noise stimuli reveals that conduction velocity and response latency are negatively correlated. Conclusion/Significance: Intraretinal conduction does not change the relative spike timing between ganglion cells of the same type but increases spike timing differences among ganglion cells of different type. The fastest retinal ganglion cells therefore act as indicators of new stimuli for postsynaptic neurons. The intraretinal dispersion of the population activity will not be compensated by variability in extraretinal conduction times, estimated from data in the literature