Diagnostic value of cone beam computed tomography for root canal morphology assessment - a micro-CT based comparison.

OBJECTIVES: The aim of this study was to assess cone beam computed tomography (CBCT) as a root canal anatomy diagnostic tool by comparison with micro-CT gold-standard. MATERIALS AND METHODS: 216 two-rooted mandibular molars were first scanned in a CBCT device (200 µm voxel size) and posteriorly in a micro-CT scanner (19.61 µm). The volumes were sequentially screened to classify main root canal anatomy according to Vertucci classification, and for the presence of lateral canals and apical deltas, in both mesial and distal roots. RESULTS: Both methods revealed a higher prevalence of Vertucci Type II and IV in the mesial root, and Vertucci Type I in the distal root. The percentage of agreement for main root canal anatomy classification between CBCT and micro-CT scores was high (85.2%). CONCLUSION: Sensibility to detect both lateral canals and apical deltas with CBCT was low. These results attest to the fact that minor anatomical changes might be difficult to identify with CBCT imaging, hampering its diagnostic value.

quincunx: an R package to query, download and wrangle PGS Catalog data.

MOTIVATION: The Polygenic Score (PGS) Catalog is a recently established open database of published polygenic scores that, to date, has collected, curated and made available 721 polygenic scores from over 133 publications. The PGS Catalog REST API is the only method allowing programmatic access to this resource. RESULTS: Here, we describe quincunx, an R package that provides the first client interface to the PGS Catalog REST API. quincunx enables users to query and quickly retrieve, filter and integrate metadata associated with polygenic scores, as well as polygenic scoring files in tidy table format. AVAILABILITY AND IMPLEMENTATION: quincunx is freely available under an MIT License, and can be accessed from https://github.com/maialab/quincunx. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Detection and molecular characterization of a new genotype of infectious bursal disease virus in Portugal.

RESEARCH HIGHLIGHTSEight IBDV strains with unique VP2 features were detected in Portugal.Based on two distinct classification methods, the strains belong to a new genotype.

Alternate Wetting and Drying in the Center of Portugal: Effects on Water and Rice Productivity and Contribution to Development.

Rice irrigation by continuous flooding is highly water demanding in comparison with most methods applied in the irrigation of other crops, due to a significant deep percolation and surface drainage of paddies. The pollution of water resources and methane emissions are other environmental problems of rice agroecosystems, which require effective agronomic changes to safeguard its sustainable production. To contribute to this solution, an experimental study of alternate wetting and drying flooding (AWD) was carried out in the Center of Portugal in farmer's paddies, using the methodology of field irrigation evaluation. The AWD results showed that there is a relevant potential to save about 10% of irrigation water with a reduced yield impact, allowing an additional period of about 10 to 29 days of dry soil. The guidelines to promote the on-farm scale AWD automation were outlined, integrating multiple data sources, to get a safe control of soil water and crop productivity. The conclusions point out the advantages of a significant change in the irrigation procedures, the use of water level sensors to assess the right irrigation scheduling to manage the soil deficit and the mild crop stress during the dry periods, and the development of paddy irrigation supplies, to allow a safe and smart AWD.

Successful metabolic control in diabetes type 1 depends on individual neuroeconomic and health risk-taking decision endophenotypes: a new target in personalized care.

BACKGROUND: Neurobehavioral decision profiles have often been neglected in chronic diseases despite their direct impact on major public health issues such as treatment adherence. This remains a major concern in diabetes, despite intensive efforts and public awareness initiatives regarding its complications. We hypothesized that high rates of low adherence are related to risk-taking profiles associated with decision-making phenotypes. If this hypothesis is correct, it should be possible to define these endophenotypes independently based both on dynamic measures of metabolic control (HbA1C) and multidimensional behavioral profiles. METHODS: In this study, 91 participants with early-stage type 1 diabetes fulfilled a battery of self-reported real-world risk behaviors and they performed an experimental task, the Balloon Analogue Risk Task (BART). RESULTS: K-means and two-step cluster analysis suggest a two-cluster solution providing information of distinct decision profiles (concerning multiple domains of risk-taking behavior) which almost perfectly match the biological partition, based on the division between stable or improving metabolic control (MC, N = 49) v. unstably high or deteriorating states (NoMC, N = 42). This surprising dichotomy of behavioral phenotypes predicted by the dynamics of HbA1C was further corroborated by standard statistical testing. Finally, the BART game enabled to identify groups differences in feedback learning and consequent behavioral choices under ambiguity, showing distinct group choice behavioral patterns. CONCLUSIONS: These findings suggest that distinct biobehavioral endophenotypes can be related to the success of metabolic control. These findings also have strong implications for programs to improve patient adherence, directly addressing risk-taking profiles.

Reading and Calculation Neural Systems and Their Weighted Adaptive Use for Programming Skills.

Software programming is a modern activity that poses strong challenges to the human brain. The neural mechanisms that support this novel cognitive faculty are still unknown. On the other hand, reading and calculation abilities represent slightly less recent human activities, in which neural correlates are relatively well understood. We hypothesize that calculus and reading brain networks provide joint underpinnings with distinctly weighted contributions which concern programming tasks, in particular concerning error identification. Based on a meta-analysis of the core regions involved in both reading and math and recent experimental evidence on the neural basis of programming tasks, we provide a theoretical account that integrates the role of these networks in program understanding. In this connectivity-based framework, error-monitoring processing regions in the frontal cortex influence the insula, which is a pivotal hub within the salience network, leading into efficient causal modulation of parietal networks involved in reading and mathematical operations. The core role of the anterior insula and anterior midcingulate cortex is illuminated by their relation to performance in error processing and novelty. The larger similarity that we observed between the networks underlying calculus and programming skills does not exclude a more limited but clear overlap with the reading network, albeit with differences in hemispheric lateralization when compared with prose reading. Future work should further elucidate whether other features of computer program understanding also use distinct weights of phylogenetically "older systems" for this recent human activity, based on the adjusting influence of fronto-insular networks. By unraveling the neural correlates of program understanding and bug detection, this work provides a framework to understand error monitoring in this novel complex faculty.

Continuous theta burst stimulation increases contralateral mu and beta rhythms with arm elevation: implications for neurorehabilitation.

The study of the physiological effects underlying brain response to transcranial magnetic stimulation is important to understand its impact on neurorehabilitation. We aim to analyze the impact of a transcranial magnetic stimulation protocol, the continuous theta burst (cTBS), on human neurophysiology, particularly on contralateral motor rhythms. cTBS was applied in 20 subjects over the primary motor cortex. We recorded brain electrical activity pre- and post-cTBS with electroencephalography both at rest and while performing motor tasks, to evaluate changes in brain oscillatory patterns such as mu and beta rhythms. Moreover, we measured motor-evoked potentials before and after cTBS to assess its impact on brain's excitability. On the hemisphere contralateral to the protocol, we did observe a significant increase in mu (p = 0.027) and beta (p = 0.006) rhythms from pre- to post-cTBS, at the beginning of arm elevation. The topology of action planning and motor execution suggests that cTBS produced an inhibitory effect that propagated to the contralateral hemisphere, thereby precluding the expected/desired excitation for therapy purposes. This novel approach provides support for the notion that this protocol induces inhibitory changes in contralateral motor rhythms, by decreasing desynchronization, contradicting the ipsilateral inhibition vs. contralateral disinhibition hypothesis. Our results have implications for personalized cTBS usage as a rehabilitation intervention, suggesting that an unexpected propagation of inhibition can occur.

StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs. It is based on careful selection, standardized processing and stringent quality control of relevant transcriptomics datasets to minimize artefacts, and includes currently over 960 transcriptomes covering a broad range of SC types. Each of the integrated datasets was individually inspected and manually curated. StemMapper's user-friendly interface enables fast querying, comparison, and interactive visualization of quality-controlled SC gene expression data in a comprehensive manner. A proof-of-principle analysis discovering novel putative astrocyte/neural SC lineage markers exemplifies the utility of the integrated data resource. We believe that StemMapper can open the way for new insights and advances in SC research by greatly simplifying the access and analysis of SC transcriptomic data. StemMapper is freely accessible at http://stemmapper.sysbiolab.eu.

Transcranial Magnetic Stimulation as an Intervention Tool to Recover from Language, Swallowing and Attentional Deficits after Stroke: A Systematic Review.

BACKGROUND: Following a stroke event, patients often are severely affected by disabilities that hinder their quality-of-life. There are currently several rehabilitative options and strategies, and it is crucial to find the most effective interventions. The applicability of transcranial magnetic stimulation (TMS) to the recovery of nonmotor functions such as communication skills, swallowing ability and spatial attention after stroke remains important clinical questions. SUMMARY: We searched PubMed and ISI Web of Science for articles that used repetitive TMS protocols to rehabilitate post-stroke deficits. We analysed qualitatively 38 articles that met the eligibility criteria; of these, 21 dealt with aphasia, 8 with dysphagia, 8 with neglect and 1 with visual extinction. The efficacy of TMS as an intervention for post-stroke rehabilitation of these nonmotor deficits was studied as well as the current limitations were assessed. Key Messages: Most part of the included studies reported statistically significant functional improvements, supporting the use of TMS for the rehabilitation of aphasia, dysphagia and neglect. Future research, with larger sample sizes, is mandatory to confirm its efficacy, determine the optimal stimulation parameters and investigate inter-subject variability.

The Use of Repetitive Transcranial Magnetic Stimulation for Stroke Rehabilitation: A Systematic Review.

OBJECTIVES: Stroke is a leading cause of disability. Alternative and more effective techniques for stroke rehabilitation have been sought to overcome limitations of conventional therapies. Repetitive transcranial magnetic stimulation (rTMS) arises as a promising tool in this context. This systematic review aims to provide a state of the art on the application of rTMS in stroke patients and to assess its effectiveness in clinical rehabilitation of motor function. METHODS: Studies included in this review were identified by searching PubMed and ISI Web of Science. The search terms were (rTMS OR "repetitive transcranial magnetic stimulation") AND (stroke OR "cerebrovascular accident" OR CVA) AND (rehab OR rehabilitation OR recover*). The retrieved records were assessed for eligibility and the most relevant features extracted to a summary table. RESULTS: Seventy out of 691 records were deemed eligible, according to the selection criteria. The majority of the articles report rTMS showing potential in improving motor function, although some negative reports, all from randomized controlled trials, contradict this claim. Future studies are needed because there is a possibility that a bias for non-publication of negative results may be present. CONCLUSIONS: rTMS has been shown to be a promising tool for stroke rehabilitation, in spite of the lack of standard operational procedures and harmonization. Efforts should be devoted to provide a greater understanding of the underlying mechanisms and protocol standardization.

The intestinal proteome of diabetic and control children is enriched with different microbial and host proteins.

In this study, the intestinal microbial proteome of children with established type 1 diabetes (T1D) was compared with the proteome of healthy children (Control) with the aim to identify differences in the activity of the intestinal microbiota that not only will contribute to a deeper knowledge of the functionality of the gut in these children but also may provide new approaches to improve the control of the disease. Faecal protein extracts collected from three T1D children (aged 9.3±0.6 years) and three Control children (aged 9.3±1.5 years) were analysed using a combination of 2D gel electrophoresis and spectral counting. The results evidenced markedly differences between the intestinal proteome of T1D children and the Control. The T1D microbial intestinal proteome was enriched with proteins of clostridial cluster XVa and cluster IV and Bacteroides. In contrast, the Control proteome was enriched with bifidobacterial proteins. In both groups, proteins with moonlight function were observed. Human proteins also distinguished the two groups with T1D children depleted in exocrine pancreatic enzymes.

StemChecker: a web-based tool to discover and explore stemness signatures in gene sets.

Stem cells present unique regenerative abilities, offering great potential for treatment of prevalent pathologies such as diabetes, neurodegenerative and heart diseases. Various research groups dedicated significant effort to identify sets of genes-so-called stemness signatures-considered essential to define stem cells. However, their usage has been hindered by the lack of comprehensive resources and easy-to-use tools. For this we developed StemChecker, a novel stemness analysis tool, based on the curation of nearly fifty published stemness signatures defined by gene expression, RNAi screens, Transcription Factor (TF) binding sites, literature reviews and computational approaches. StemChecker allows researchers to explore the presence of stemness signatures in user-defined gene sets, without carrying-out lengthy literature curation or data processing. To assist in exploring underlying regulatory mechanisms, we collected over 80 target gene sets of TFs associated with pluri- or multipotency. StemChecker presents an intuitive graphical display, as well as detailed statistical results in table format, which helps revealing transcriptionally regulatory programs, indicating the putative involvement of stemness-associated processes in diseases like cancer. Overall, StemChecker substantially expands the available repertoire of online tools, designed to assist the stem cell biology, developmental biology, regenerative medicine and human disease research community. StemChecker is freely accessible at http://stemchecker.sysbiolab.eu.

European cowpea landraces for a more sustainable agriculture system and novel foods.

BACKGROUND: Genetic diversity is fundamental to breeding programs and consequently has an important role in obtaining new varieties. To properly use the genetic diversity present in germplasm collections, a good knowledge of the agro-morphological traits of each accession is needed. The aim of this study was to explore the production capacity of 24 cowpea landraces from southern Europe, through phenotypic characterization and evaluation in three different locations in Greece and Portugal. RESULTS: Most qualitative parameters tested showed a high stability among the three locations. A wide difference was observed among the three locations with respect to number of days to flowering, ranging from 55 to 99 days. Quantitative traits showed a higher genotype × environment than genetic variance component. In general, an inverse relationship between σ2ge /σ2g ratio (where σ2ge is genotype × genotype interaction and σ2g is genotype impact) and heritability value was observed. Principal component analysis was able to group accessions based on their origin. The first two principal components explained 97.52% of variation, being the number of seeds per plant, plant height and seed protein content, the traits which contributed most to variability. CONCLUSION: The results show that sufficient variation exists in different traits within landraces in the studied cowpea germplasm to pursue a breeding program. However, the quantitative traits showed a higher genotype × environment component. © 2017 Society of Chemical Industry.

Antibiotic resistance in wastewater: occurrence and fate of Enterobacteriaceae producers of class A and class C ß-lactamases.

Antibiotics have been intensively used over the last decades in human and animal therapy and livestock, resulting in serious environmental and public health problems, namely due to the antibiotic residues concentration in wastewaters and to the development of antibiotic-resistant bacteria. This study aimed to access the contribution of some anthropological activities, namely urban household, hospital and a wastewater treatment plant, to the spread of antibiotic resistances in the treated wastewater released into the Mondego River, Coimbra, Portugal. Six sampling sites were selected in the wastewater network and in the river. The ampicillin-resistant Enterobacteriaceae of the water samples were enumerated, isolated and phenotypically characterized in relation to their resistance profile to 13 antibiotics. Some isolates were identified into species level and investigated for the presence of class A and class C -lactamases. Results revealed high frequency of resistance to the -lactam group, cefoxitin (53.5%), amoxicillin/clavulanic acid combination (43.5%), cefotaxime (22.7%), aztreonam (21.3) cefpirome (19.2%), ceftazidime (16.2%) and to the non--lactam group, trimethoprim/sulfamethoxazol (21.1%), tetracycline (18.2%), followed by ciprofloxacin (14.1%). The hospital effluent showed the higher rates of resistance to all antibiotic, except two (chloramphenicol and gentamicin). Similarly, higher resistance rates were detected in the wastewater treatment plant (WWTP) effluent compared with the untreated affluent. Regarding the multidrug resistance, the highest incidence was recorded in the hospital sewage and the lowest in the urban waste. The majority of the isolates altogether are potentially extended-spectrum -lactamases positive (ESBL(+)) (51.9%), followed by AmpC(+) (44.4%) and ESBL(+)/AmpC(+) (35.2%). The most prevalent genes among the potential ESBL producers were blaOXA (33.3%), blaTEM (24.1%) and blaCTX-M (5.6%) and among the AmpC producers were blaEBC (38.9%), blaFOX (1.9%) and blaCIT (1.9%). In conclusion, the hospital and the WWTP activities revealed to have the highest contribution to the spread of multidrug resistant bacteria in the study area. Such data is important for future management of the environmental and public health risk of these contaminants. This is the first embracing study in the water network of Coimbra region on the dissemination of antibiotic resistance determinants. Moreover, it is also the first report with the simultaneous detection of multiresistant bacteria producers of AmpC and ESBLs -lactamases in aquatic systems in Portugal.

Loss, replacement and gain of proteins at the origin of the mitochondria.

We review what has been inferred about the changes at the level of the proteome that accompanied the evolution of the mitochondrion from an alphaproteobacterium. We regard these changes from an alphaproteobacterial perspective: which proteins were lost during mitochondrial evolution? And, of the proteins that were lost, which ones have been replaced by other, non-orthologous proteins with a similar function? Combining literature-supported replacements with quantitative analyses of mitochondrial proteomics data we infer that most of the loss and replacements that separate current day mitochondria in mammals from alphaproteobacteria took place before the radiation of the eukaryotes. Recent analyses show that also the acquisition of new proteins to the large protein complexes of the oxidative phosphorylation and the mitochondrial ribosome occurred mainly before the divergence of the eukaryotes. These results indicate a significant number of pivotal evolutionary events between the acquisition of the endosymbiont and the radiation of the eukaryotes and therewith support an early acquisition of mitochondria in eukaryotic evolution. Technically, advancements in the reconstruction of the evolutionary trajectories of loss, replacement and gain of mitochondrial proteins depend on using profile-based homology detection methods for sequence analysis. We highlight the mitochondrial Holliday junction resolvase endonuclease, for which such methods have detected new "family members" and in which function differentiation is accompanied by the loss of catalytic residues for the original enzymatic function and the gain of a protein domain for the new function. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems.

The dual facet of gamma oscillations: separate visual and decision making circuits as revealed by simultaneous EEG/fMRI.

It remains an outstanding question whether gamma-band oscillations reflect unitary cognitive processes within the same task. EEG/MEG studies do lack the resolution or coverage to address the highly debated question whether single gamma activity patterns are linked with multiple cognitive modules or alternatively each pattern associates with a specific cognitive module, within the same coherent perceptual task. One way to disentangle these issues would be to provide direct identification of their sources, by combining different techniques. Here, we directly examined these questions by performing simultaneous EEG/fMRI using an ambiguous perception paradigm requiring holistic integration. We found that distinct gamma frequency sub-bands reflect different neural substrates and cognitive mechanisms when comparing object perception states vs. no categorical perception. A low gamma sub-band (near 40 Hz) activity was tightly related to the decision making network, and in particular the anterior insula. A high gamma sub-band (∼60 Hz) could be linked to early visual processing regions. The demonstration of a clear functional topography for distinct gamma sub-bands within the same task shows that distinct gamma-band modulations underlie sensory processing and perceptual decision mechanisms.

Trust-based health decision-making recruits the neural interoceptive saliency network which relates to temporal trajectories of Hemoglobin A1C in Diabetes Type 1.

Experimental approaches in neuroeconomics generally involve monetary utility. Utility in the health domain is relevant in diabetes because constant daily life decisions are critical for self-consequential long-term outcomes. We used fMRI to investigate self-consequent decision-making in the health and economic domains in Type 1 Diabetes Mellitus and controls (N = 50). We focused on two critical phases of decision-making: Investment and Feedback (Positive or Negative). Patients showed larger BOLD activation of limbic, and reward/dopaminergic regions in particular in the health trust game. Importantly, the worse the trajectory of metabolic control (increasing HbA1C), the higher the BOLD activity in regions of the interoceptive saliency network. This was manifested by positive correlations between brain activity during investment in anterior cingulate cortex and insula and HbA1c blood level progression. We conclude that the neural correlates of health-consequent decision-making domain involve limbic and reward related dopaminergic regions in Type 1 Diabetes Mellitus. Furthermore, the temporal trajectory of HbA1C blood levels is correlated with neural risk processing in the saliency network. Evidence for differential risk processing in the health versus the neuroeconomic context, and the discovery of a role for the saliency interoceptive network in metabolic control trajectories suggests a new perspective on the development of personalized interventions.

Neural inhibition as implemented by an actor-critic model involves the human dorsal striatum and ventral tegmental area.

Inhibition is implicated across virtually all human experiences. As a trade-off of being very efficient, this executive function is also prone to many errors. Rodent and computational studies show that midbrain regions play crucial roles during errors by sending dopaminergic learning signals to the basal ganglia for behavioural adjustment. However, the parallels between animal and human neural anatomy and function are not determined. We scanned human adults while they performed an fMRI inhibitory task requiring trial-and-error learning. Guided by an actor-critic model, our results implicate the dorsal striatum and the ventral tegmental area as the actor and the critic, respectively. Using a multilevel and dimensional approach, we also demonstrate a link between midbrain and striatum circuit activity, inhibitory performance, and self-reported autistic and obsessive-compulsive subclinical traits.

Syringe irrigation in confluent canals: A sequential computational fluid dynamics assessment.

This study aims to assess the influence of root canal preparation, irrigation needle design and its placement depth in the irrigation flow of confluent canals during syringe irrigation. A mandibular molar presenting two confluent canals in its mesial root was sequentially prepared and scanned by micro-computed tomography after mechanical preparation up to ProTaper Next system sizes X2 (25/.06v), X3 (30/.07v) and X4 (40/.06v). In each of the root canal preparation models, a side-vented and an open-ended needle at 5, 3 and 2 mm from the working length were included, and irrigation flow was assessed by a validated computational fluid dynamics model. The results revealed that the irrigant flowed out of the confluent canals mainly through the canal that did not have the needle. Apical penetration and renewal of the irrigant were most efficiently achieved with the use of a 30G open-ended needle and a 30/.07v preparation.

Neural underpinnings of ethical decisions in life and death dilemmas in naïve and expert firefighters.

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas.