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Postoperative nausea and vomiting (PONV) occurs in up to 30% of patients and its pathophysiology and mechanisms have not been completely described. Hypotension and a decrease in cardiac output are suspected to induce nausea. The hypothesis that intraoperative hypotension might influence the incidence of PONV was investigated. The study was conducted as a retrospective large single center cohort study. The incidence of PONV was investigated until discharge from post anesthesia care unit (PACU). Surgical patients with general anesthesia during a 2-year period between 2018 and 2019 at a university hospital in Germany were included. Groups were defined based on the lowest documented mean arterial pressure (MAP) with group H50: MAP <50mmHg; group H60: MAP <60mmHg; group H70: MAP <70mmHg, and group H0: no MAP <70mmHg. Decreases of MAP in the different groups were related to PONV. Propensity-score matching was carried out to control for overlapping risk factors. In the 2-year period 18.674 patients fit the inclusion criteria. The overall incidence of PONV was 11%. Patients with hypotension had a significantly increased incidence of PONV (H0 vs. H50: 11.0% vs.17.4%, Risk Ratio (RR): 1.285 (99%CI: 1.102–1.498), p < 0.001; H0 vs. H60: 10.4% vs. 13.5%, RR: 1.1852 (99%CI: 1.0665–1.3172), p < 0.001; H0 vs. H70: 9.4% vs. 11.2%, RR: 1.1236 (99%CI: 1.013 − 1.2454); p = 0.0027). The study demonstrates an association between intraoperative hypotension and early PONV. A more severe decrease of MAP had a pronounced effect. [ABSTRACT FROM AUTHOR]

When different researchers study the same research question using the same dataset they may obtain different and potentially even conflicting results. This is because there is often substantial flexibility in researchers' analytical choices, an issue also referred to as "researcher degrees of freedom". Combined with selective reporting of the smallest p-value or largest effect, researcher degrees of freedom may lead to an increased rate of false positive and overoptimistic results. In this paper, we address this issue by formalizing the multiplicity of analysis strategies as a multiple testing problem. As the test statistics of different analysis strategies are usually highly dependent, a naive approach such as the Bonferroni correction is inappropriate because it leads to an unacceptable loss of power. Instead, we propose using the "minP" adjustment method, which takes potential test dependencies into account and approximates the underlying null distribution of the minimal p-value through a permutation-based procedure. This procedure is known to achieve more power than simpler approaches while ensuring a weak control of the family-wise error rate. We illustrate our approach for addressing researcher degrees of freedom by applying it to a study on the impact of perioperative p a O 2 on post-operative complications after neurosurgery. A total of 48 analysis strategies are considered and adjusted using the minP procedure. This approach allows to selectively report the result of the analysis strategy yielding the most convincing evidence, while controlling the type 1 error—and thus the risk of publishing false positive results that may not be replicable. [ABSTRACT FROM AUTHOR]

Disturbances in the sleep–wake cycle are a debilitating, yet rather common condition not only in humans, but also in family dogs. While there is an emerging need for easy-to-use tools to document sleep alterations (in order to ultimately treat and/or prevent them), the veterinary tools which yield objective data (e.g. polysomnography, activity monitors) are both labor intensive and expensive. In this study, we developed a modified version of a previously used sleep questionnaire (SNoRE) and determined criterion validity in companion dogs against polysomnography and physical activity monitors (PAMs). Since a negative correlation between sleep time and cognitive performance in senior dogs has been demonstrated, we evaluated the correlation between the SNoRE scores and the Canine Dementia Scale (CADES, which includes a factor concerning sleep). There was a significant correlation between SNoRE 3.0 questionnaire scores and polysomnography data (latency to NREM sleep, ρ = 0.507, p < 0.001) as well as PAMs' data (activity between 1:00 and 3:00 AM, p < 0.05). There was a moderate positive correlation between the SNoRE 3.0 scores and the CADES scores (ρ = 0.625, p < 0.001). Additionally, the questionnaire structure was validated by a confirmatory factor analysis, and it also showed an adequate test–retest reliability. In conclusion the present paper describes a valid and reliable questionnaire tool, that can be used as a cost-effective way to monitor dog sleep in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Reverse-transcribed gene copies (retrocopies) have emerged as major sources of evolutionary novelty. MicroRNAs (miRNAs) are small and highly conserved RNA molecules that serve as key post-transcriptional regulators of gene expression. The origin and subsequent evolution of miRNAs have been addressed but not fully elucidated. Results: In this study, we performed a comprehensive investigation of miRNA origination through retroduplicated mRNA sequences (retro-miRs). We identified 17 retro-miRs that emerged from the mRNA retrocopies. Four of these retro-miRs had de novo origins within retrocopied sequences, while 13 retro-miRNAs were located within exon regions and duplicated along with their host mRNAs. We found that retro-miRs were primate-specific, including five retro-miRs conserved among all primates and two human-specific retro-miRs. All retro-miRs were expressed, with predicted and experimentally validated target genes except miR-10527. Notably, the target genes of retro-miRs are involved in key biological processes such as metabolic processes, cell signaling, and regulation of neurotransmitters in the central nervous system. Additionally, we found that these retro-miRs play a potential oncogenic role in cancer by targeting key cancer genes and are overexpressed in several cancer types, including liver hepatocellular carcinoma and stomach adenocarcinoma. Conclusions: Our findings demonstrated that mRNA retrotransposition is a key mechanism for the generation of novel miRNAs (retro-miRs) in primates. These retro-miRs are expressed, conserved, have target genes with important cellular functions, and play important roles in cancer. [ABSTRACT FROM AUTHOR]

Time-dependent traffic speed information at a street level is important for routing services to estimate accurate travel times and to recommend routes which avoid traffic congestion. Still, most open-source routing machines that use OpenStreetMap (OSM) as the primary data source rely on static driving speeds derived from OSM tags, since comprehensive traffic speed data is not openly available. In this study, a method was developed to model traffic speed by hour of day at a street level using open data from OpenStreetMap, Twitter and population data. The modelled traffic speed data was subsequently integrated into the open-source routing engine openrouteservice to improve travel time estimation in route planning. Machine learning models were trained for ten cities worldwide using traffic speed data from Uber Movement as reference data. Different indicators based on geolocation and timestamp of Twitter data as well as a geographically adapted betweeness centrality indicator were evaluated for their potential to improve prediction accuracy. In all cities, the Twitter indicators improved the model, although this effect was only visible for certain road types. The centrality indicator improved the model as well but to a lesser extent. The Google Routing API was used as reference to evaluate the accuracy in travel time estimation. Deviations in travel times were regionally different and were partly alleviated by including the raw traffic data by Uber or the modelled traffic speed data in openrouteservice. [ABSTRACT FROM AUTHOR]

Rationale: Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.Objectives: We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.Methods: An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC-MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.Measurements and Main Results: Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70-0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.Conclusions: In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.Clinicaltrials: gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254 . [ABSTRACT FROM AUTHOR]

Urban green spaces (UGSs) can provide important ecosystem services for citizens and their well-being. To make use of these services according to UGS user demands, urban residents, tourists, and city administrations should know where UGSs are located, what qualities they have and how to reach them on convenient routes. This paper presents a novel digital infrastructure which combines and fuses different data to map UGSs and their qualities, and makes this information available in a web app. The interactive information service of the app aims to support citizens to explore and search for suitable UGSs and to provide routing options to reach them based on their preferences. Via implicit and explicit feedback functions included in the app, further information on UGS users' preferences can be collected to enhance the overall knowledge basis, while respecting data privacy issues. The underlying data base consists primarily of open and volunteered geographic data, which allows for transferability to other cities. This paper describes the system design, its back-end and front-end components, as well as the process of development and deployment of the system in two pilot cities. Preliminary results of the piloting in the two cities are presented, focusing on user preferences for UGSs searches. The added value of the web app for city residents and the role of the newly gained knowledge for urban planning is discussed and reflected upon. [ABSTRACT FROM AUTHOR]

Objective: To utilize, in an individual and institutional privacy-preserving manner, electronic health record (EHR) data from 202 hospitals by analyzing answers to COVID-19-related questions and posting these answers online.Materials and Methods: We developed a distributed, federated network of 12 health systems that harmonized their EHRs and submitted aggregate answers to consortia questions posted at https://www.covid19questions.org. Our consortium developed processes and implemented distributed algorithms to produce answers to a variety of questions. We were able to generate counts, descriptive statistics, and build a multivariate, iterative regression model without centralizing individual-level data.Results: Our public website contains answers to various clinical questions, a web form for users to ask questions in natural language, and a list of items that are currently pending responses. The results show, for example, that patients who were taking angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, within the year before admission, had lower unadjusted in-hospital mortality rates. We also showed that, when adjusted for, age, sex, and ethnicity were not significantly associated with mortality. We demonstrated that it is possible to answer questions about COVID-19 using EHR data from systems that have different policies and must follow various regulations, without moving data out of their health systems.Discussion and Conclusions: We present an alternative or a complement to centralized COVID-19 registries of EHR data. We can use multivariate distributed logistic regression on observations recorded in the process of care to generate results without transferring individual-level data outside the health systems. [ABSTRACT FROM AUTHOR]

We report on the precise manipulation of the fine structures of toroidal-spiral particles (TSPs) generated by a self-assembly process of droplet sedimentation at low Reynolds numbers in a miscible bulk solution followed by solidification. The biocompatible polymeric TSP can serve as a device for drug delivery and in vivo therapeutic cell expansion, activation, and delivery, for which highly tunable and reproducible structures are essential to design dosages and release kinetics. TSP formation can be divided into two stages: initial infusion of the drop vs its subsequent sedimentation, deformation, and entrainment of the surrounding bulk solution. The infusion rate affects the drop shape and tail length. These two features represent crucial initial conditions for subsequent shape evolution, which determines the overall morphology of the TSP and fine structure of the internal channel. Our computer simulations of drop dynamics add a new capability to the swarm-of-Stokeslets technique: unequal viscosities of the drop and bulk phases (i.e., non-unit viscosity ratio). During sedimentation, the density difference between the droplet and the bulk solution played a more pronounced role than the viscosity ratio, which was revealed both by experimental observations and numerical simulations. Understanding the fundamental hydrodynamics and developing a flow map will ultimately aid in the design of TSPs with tunable empty channels toward drug delivery and cell encapsulation. [ABSTRACT FROM AUTHOR]

There is growing interest in harnessing the genetic and adaptive diversity of crop wild relatives to improve drought resilience of elite cultivars. Rainfall gradients exert strong selection pressure on both natural and agricultural ecosystems. Understanding plant responses to these facilitates crop improvement.Wild and domesticated narrow‐leafed lupin (NLL) collected along Mediterranean terminal drought stress gradients was evaluated under contrasting reproductive phase water supply in controlled field, glasshouse and cabinet studies. Plant phenology, growth and productivity, water use and stress responses were measured over time.There is an integrated suite of adaptive changes along rainfall gradients in NLL. Low rainfall ecotypes flower earlier, accumulate lower seed numbers, biomass and leaf area, and have larger root:shoot ratios than high rainfall ecotypes. Water‐use is lower and stress onset slower in low compared to high rainfall ecotypes. Water‐use rates and ecotypic differences in stress response (Ψleaf decline, leaf loss) are lower in NLL than yellow lupin (YL). To mitigate the effects of profligate water use, high rainfall YL ecotypes maintain higher leaf water content over declining leaf water potential than low rainfall ecotypes. There is no evidence for such specific adaptation in NLL.The data suggests that appropriate phenology is the key adaptive trait to rainfall gradients in NLL because of the flow‐on effects on biomass production, fitness, transpiration and stress onset, and the lack of physiological adaptations as in YL. Accordingly, it is essential to match phenology with target environment in order to minimize risk and maximize yield potential. [ABSTRACT FROM AUTHOR]

To celebrate the tenth anniversary of InterPore, we present an interdisciplinary review of colloid transport through porous media. This review aims to explore both classical colloid transport and topics that fall outside that purview and thus offer transformative insights into the physics governing transport behavior. First, we discuss the unique colloid characteristics relative to molecules and larger particles. Then, the classical advection–dispersion–filtration models (both conceptual and mathematical) of colloid transport are introduced as well as anomalous transport behaviors. Next, the forces of interaction between colloids and porous media surfaces are discussed. Fourth, applications that are interested in maximizing the transport of colloids through porous media are considered. Then the concept of motile, active biocolloids is introduced, and finally, colloid swarming as a newly recognized mode of transport is summarized. [ABSTRACT FROM AUTHOR]

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Introduction The pan-Canadian Oncology Symptom Triage and Remote Support (costars) team is studying how to improve the quality and consistency of cancer symptom management. Methods A 1-day invitational meeting was held 24 October 2017 in Ottawa, Ontario, to review the current evidence from costars projects and to establish research priorities for a future largescale implementation study. The meeting included 36 participants who were clinicians from adult oncology, pediatric oncology, and homecare; policymakers from national, provincial, and regional organizations; researchers; and a patient. Half the day involved summarizing evidence from four costars studies and experiences with implementing the costars symptom practice guides. The second half of the day used a modified nominal group technique to generate research questions within small groups, presentation of research questions to all participants, and two rounds of voting to reach consensus on research priorities. Results Participants proposed 4 research categories: ■ User-centred augmentation to enhance usability (for example, designing a mobile costars solution) ■ Outcome measurement (for example, determining key competencies for clinicians) ■ Regular renewal of costars to keep pace with evolving evidence (for example, updates for novel therapies) ■ Integration into clinical practice (for example, meaningful engagement of patients and caregivers in study design). Conclusions Across categories, the top 3 priorities were effect on health services use, competency development, and a mobile costars solution. Future research will address identified priorities, reflecting the needs and perspectives of diverse stakeholders. Stakeholder collaboration will continue to guide our approach to operationalizing this priority research agenda. [ABSTRACT FROM AUTHOR]

Aims: Coagulase‐negative Staphylococcus xylosus strains are used as starter organisms for sausage fermentation. As those strains have to cope with low pH‐values during fermentation, the aim of this study was to identify the acid adaptation mechanisms of S. xylosus TMW 2.1523 previously isolated from salami. Methods and Results: A comparative proteomic study between two different acid tolerant mutants was performed. Therefore, both S. xylosus mutants were grown pH‐static under acid stress (pH 5·1) and reference conditions (pH 7·0). Proteomic data were supported by metabolite and cell membrane lipid analysis. Staphylococcus xylosus acid stress adaptation is mainly characterized by a metabolic change towards neutral metabolites, enhanced urease activity, reduced ATP consumption, an increase in membrane fluidity and changes in the membrane thickness. Conclusion: This study corroborates mechanisms as previously described for other Gram‐positive bacteria. Additionally, the adjustment of membrane structure and composition in S. xylosus TMW 2.1523 play a prominent role in its acid adaptation. Significance and Impact of the Study: This study demonstrates for the first time changes in the membrane lipid composition due to acid stress adaptation in staphylococci. [ABSTRACT FROM AUTHOR]

Background Radiation therapists play an important role in helping patients to safely manage and triage potentially life-threatening symptoms. The purpose of the present study was to assess factors influencing the use by radiation therapists of evidence-informed symptom practice guides for patients experiencing cancer treatment–related symptoms. Methods In a mixed-methods descriptive study guided by the Knowledge-to-Action framework, interviews and a barriers survey were conducted. Two independent reviewers conducted a content analysis of interview transcripts. Barriers survey data were analyzed using frequency distributions and univariate descriptive statistics. Open-ended data from the surveys underwent content analysis and were triangulated with interview findings. Results Of 90 radiation therapists approached, 58 completed the survey (64%), and 14 were interviewed. Of the 98% who reported providing symptom management to patients undergoing radiation treatment, 53% used evidence-informed practice guidelines. Radiation therapists had moderate moral norms (4.6 of 7) and beliefs about the consequences of using costars (pan-Canadian Oncology Symptom Triage and Remote Support) practice guides (4.8), but neutral intention (3.4) and beliefs about their own capabilities (3.9). Environmental barriers included lack of time (2.0), lack of access (2.5), and neutral organizational support (3.0). Radiation therapists identified a need for training (5.5). Common unique barriers to practice guide use were lack of time during radiation treatments, unclear fit with scope of practice, disparate focus on site-specific symptoms, and lack of medication knowledge. Conclusions The symptom practice guides were perceived by the radiation therapists to benefit patients, enhance their own knowledge of symptom management, and promote consistent practice. Additional work is required to identify the scope of practice of radiation therapists within the interprofessional team. [ABSTRACT FROM AUTHOR]

Among the available online techniques to characterize combustion generated nanomaterials, the recently developed RDD-SMPS-ICP-MS (rotating disc diluter-scanning mobility particle sizer-inductively coupled plasma-mass spectrometry) setup is here suggested, due to its ability to provide simultaneously size-resolved elemental and quantitative information with a high time resolution. The successful calibration strategy presented in Part I will be applied here. To assess the resolving power of the technique regarding the elemental composition, two different applications with complex heterogeneous matrixes were considered: a mixture of several metal chlorides particles generated by the reaction of metal oxides (PbO, CdO, CuO, ZnO) with CaCl2·2H2O and secondary formed ZnO nano-objects released during the combustion of impregnated wood. The latter, especially, allowed considering the effect of the heterogeneous nature of a realistic process gas sample, where several gas species are emitted. The results of these experiments showed the ability of the SMPS-ICPMS system to distinguish and quantify the single contribution of a specific element in the overall particle size distribution (PSD). [ABSTRACT FROM AUTHOR]

The coupling between a scanning mobility particle sizer (SMPS) and an inductively coupled mass spectrometry (ICP-MS) was in the past shown to obtain simultaneous size-resolved and elemental information on nanoparticles, using a rotating disc diluter (RDD) as conditioning and dilution system. A calibration strategy for the hyphenated RDD-SMPS-ICP-MS setup is presented here. Evaporation experiments of ZnCl2 powder were performed at four different temperatures, using a TGA as an aerosol source to correlate linearly the weight in loss of the TGA with the averaged ICP-MS intensities measured in transient mode. The calibration curve of Zn showed a good correlation factor (R2 = 0.9985) and a sensitivity of 20.95 × 103 counts ng−1. The LoD (limit of detection) of the method was estimated to be ∼32 ng cm−3, once the total dilution of the whole setup is considered. A second set of experiments was performed, where ZnO and CaCl2·2H2O powders were used as reactants to generate ZnCl2 particles. The output data of the two instruments were treated and appropriately converted, to allow a direct and quantitative comparison between the performances of SMPS and ICP-MS. The ICP-MS signal of Zn was quantified by using the external calibration performed with the coupling of a TGA with an ICP-MS, while the SMPS volume data used two general assumptions, namely spherical morphology and bulk density of ZnCl2. Additional TEM analysis performed on the size-selected ZnCl2 particles allowed to check their morphology. The proposed calibration strategy of the ICP-MS signals enables to evaluate the SMPS quantification procedure. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims at investigating the effects of low back pain (LBP), i.e., type of symptoms, activity limitations, frequency, duration, and severity on health-related quality of life (HRQoL) in a sample of 707 community-dwelling men and women aged ≥ 65 years living in Switzerland.Methods: The study is part of a larger survey conducted in Switzerland on a sample of older adults selected randomly from population records, stratified by age and sex. The Standardized Back Pain Definition was used to investigate LBP, and HRQoL was assessed by means of the EQ-5D, including Health Utility Index (HUI) measures.Results: For more than half of the sufferers, pain was chronic, occurred most days or every day and induced activity limitations. One-third of the sufferers reported sciatica symptoms. Individuals reporting every day pain, severe pain and more than 3 years since the last episode without pain lost nearly 10 points of HRQoL. Amongst the dimension of HRQoL, Mobility was the most affected by LBP.Conclusions: These results provide further insight into the impact of qualitative aspects of LBP and in particular the importance of radiating leg pain and pain frequency and duration. While LBP-related activity limitations had little impact on both self-rated overall health and HUI, radiating leg pain and pain frequency and duration were associated with significantly decreased scores on both dimensions. [ABSTRACT FROM AUTHOR]

Motivated by the internal flow geometry of spiral-wound membrane modules with ladder-type spacers, we consider the Stokes flow singularity at a corner that joins porous and solid walls at arbitrary wedge angle Θ. Seepage flux through the porous wall is coupled to the pressure field by Darcy’s law; slip is described by a variant of the Beavers–Joseph boundary condition. On a macroscopic, outer length scale, the singularity appears like a jump discontinuity in the normal velocity, characterized by a non-integrable 1 / r divergence of the pressure. For arbitrary Θ, we develop an algebraic criterion to determine the admissible radial exponent(s) in a leading, inner similarity solution—which represents a weaker, integrable singularity in the pressure. A complete map of exponent versus Θ is provided for 0<Θ<2π: this has an intricate structure with infinitely many solution branches clustering around Θ=π and Θ=2π. By generalizing the similarity form with a (lnr) term and iterating on the slip and seepage conditions, we can carry the outer and inner power series to arbitrarily high order. Nevertheless, a numerical splice is required in between. For this purpose, we apply an iterative, numerical-asymptotic patching scheme described by Nitsche and Parthasarathi (J Fluid Mech 713:183–215, 2012). Detailed velocity and pressure profiles are calculated for three wedge angles (Θ=3π/4,π/2,π/4) and two dimensionless slip lengths (σ=20,40). The general trends for decreasing wedge angle are (i) weakening of the pressure singularity, (ii) increasing magnitude of the radial component of velocity, and (iii) movement of the inner–outer transition farther from the corner. Wedges with Θ<π are seen to differ fundamentally from the flat wedge (Θ=π) previously considered by Nitsche and Parthasarathi (2012). [ABSTRACT FROM AUTHOR]

Eukaryotic genomes frequently exhibit interdependency between transcriptional units, as evidenced by regions of high gene density. It is well recognized that vertebrate microRNAs (miRNAs) are usually embedded in those regions. Recent work has shown that the genomic context is of utmost importance to determine miRNA expression in time and space, thus affecting their evolutionary fates over long and short terms. Consequently, understanding the inter- and intraspecific changes on miRNA genomic architecture may bring novel insights on the basic cellular processes regulated by miRNAs, as well as phenotypic evolution and disease-related mechanisms. [ABSTRACT FROM AUTHOR]

Eukaryotic genomes frequently exhibit interdependency between transcriptional units, as evidenced by regions of high gene density. It is well recognized that vertebrate microRNAs (miRNAs) are usually embedded in those regions. Recent work has shown that the genomic context is of utmost importance to determine miRNA expression in time and space, thus affecting their evolutionary fates over long and short terms. Consequently, understanding the inter- and intraspecific changes on miRNA genomic architecture may bring novel insights on the basic cellular processes regulated by miRNAs, as well as phenotypic evolution and disease-related mechanisms. [ABSTRACT FROM AUTHOR]

MicroRNAs have established their role as potent regulators of the epigenome. Interestingly, most miRNAs are located within protein-coding genes with functional consequences that have yet to be fully investigated. MiRIAD is a database with an interactive and user-friendly online interface that has been facilitating research on intragenic miRNAs. In this article, we present a major update. First, data for five additional species (chimpanzee, rat, dog, cow and frog) were added to support the exploration of evolutionary aspects of the relationship between host genes and intragenic miRNAs. Moreover, we integrated data from two different sources to generate a comprehensive alternative polyadenylation dataset. The miRIAD interface was therefore redesigned and provides a completely new gene model representation, including an interactive visualization of the 30 untranslated region (UTR) with alternative polyadenylation sites, corresponding signals and potential miRNA binding sites. Furthermore, we expanded on functional host gene network analysis. Although the previous version solely reported protein interactions, the update features a separate network analysis view that can either be accessed through the submission of a list of genes of interest or directly from a gene’s list of protein interactions. In addition to statistical properties of the submitted gene set, the interaction network graph is presented and miRNAs with seed site over- and underrepresentation are identified. In summary, the update of miRIAD provides novel datasets and bioinformatics resources with a significant increase in functionality to facilitate intragenic miRNA research in a user-friendly and interactive way. [ABSTRACT FROM AUTHOR]

CONCLUSION Evidence from an unselected patient population on a nationwide basis suggests that minimally invasive mitral valve surgery is at least as safe as a full sternotomy. Keywords: Minimally invasive mitral valve surgery; Full sternotomy; Netherlands National Heart Registration EN Minimally invasive mitral valve surgery Full sternotomy Netherlands National Heart Registration 1107 1108 2 05/05/22 20220501 NES 220501 New surgical techniques and strategies need scientific analysis and evaluation of sufficiently large patient cohorts with respect to equality, possible superiority or even inferiority compared to established therapies. [Extracted from the article]

Aims The ComPath project is a pan-European programme dedicated to the monitoring of antimicrobial susceptibility of pathogens from diseased dogs and cats using standardized methods and centralized minimum inhibitory concentration ( MIC) determination. Here, the susceptibility of major pathogens is reported from antimicrobial nontreated animals with acute clinical signs of skin, wound or ear infections in 2008-2010. Methods and Results MICs were determined by agar dilution for commonly used antibiotics and interpreted using CLSI breakpoints, if available. Of the 1408 strains recovered, the main canine species was Staphylococcus pseudintermedius, followed by Pseudomonas and Streptococcus. In cats, Pasteurella multocida and Staph. pseudintermedius were most prevalent. For Staph. pseudintermedius, resistance was 18·4-25·2% for penicillin, clindamycin and chloramphenicol, but below 11% for ampicillin, amoxi/clav and fluoroquinolones. For Staphylococcus aureus, beta-lactam resistance was high (26·7-62·1%) but low (0·0-4·4%) for other antibiotics. 6·3% of Staph. pseudintermedius and 5·4% of Staph. aureus were confirmed mecA-positive. Gentamicin and fluoroquinolones exhibited moderate activity against Pseudomonas aeruginosa. For streptococci, resistance was absent/very low for penicillin, ampicillin, chloramphenicol and fluoroquinolones. For Escherichia coli, resistance was low to fluoroquinolones, chloramphenicol and gentamicin. No resistance was observed in Past. multocida. Conclusions Overall, antimicrobial resistance was low in skin and soft tissue infections in dogs and cats. The results show the need for ongoing monitoring. Significance and Impact of the Study The results are a reference baseline for future surveillance. The paucity of clinical breakpoints underlines the need to set breakpoints for relevant antibiotics. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that neuropathic pain is a neuro-immune disorder with enhanced activation of the immune system. Recent data provided proof that neuropathic pain patients exhibit increased numbers of immunosuppressive regulatory T cells (Tregs), which may represent an endogenous attempt to limit inflammation and to reduce pain levels. We here investigate the molecular mechanisms underlying these alterations.Methods: Our experimental approach includes functional analyses of primary human T cells, 3'-UTR reporter assays, and expression analyses of neuropathic pain patients' samples.Results: We demonstrate that microRNAs (miRNAs) are involved in the differentiation of Tregs in neuropathic pain. We identify miR-124a and miR-155 as direct repressors of the histone deacetylase sirtuin1 (SIRT1) in primary human CD4(+) cells. Targeting of SIRT1 by either specific siRNA or by these two miRNAs results in an increase of Foxp3 expression and, consecutively, of anti-inflammatory Tregs (siRNA: 1.7 ± 0.4; miR-124a: 1.5 ± 0.4; miR-155: 1.6 ± 0.4; p < 0.01). As compared to healthy volunteers, neuropathic pain patients exhibited an increased expression of miR-124a (2.5 ± 0.7, p < 0.05) and miR-155 (1.3 ± 0.3; p < 0.05) as well as a reduced expression of SIRT1 (0.5 ± 0.2; p < 0.01). Moreover, the expression of these two miRNAs was inversely correlated with SIRT1 transcript levels.Conclusions: Our findings suggest that in neuropathic pain, enhanced targeting of SIRT1 by miR-124a and miR-155 induces a bias of CD4(+) T cell differentiation towards Tregs, thereby limiting pain-evoking inflammation. Deciphering miRNA-target interactions that influence inflammatory pathways in neuropathic pain may contribute to the discovery of new roads towards pain amelioration.Trial Registration: German Clinical Trial Register DRKS00005954. [ABSTRACT FROM AUTHOR]

Purpose: Investigation of self-reported of low back pain (LBP) over the last month and associated health-related quality of life (HRQoL) in a sample of a community-dwelling population aged ≥65.Methods: Cross-sectional study including older adults selected randomly from population records. Data were collected within a sample stratified by age and sex. Physical and psychological healths were investigated using a standardized definition of LBP and the EuroQoL-5D for HRQoL. Analyses were first conducted on the entire sample (N = 3042) and subsequently considering the subsample who reported LBP and a paired sample drawn from the pool of LBP-free respondents.Results: 889 (29 %) respondents reported LBP within the past month, present 'most days' or 'every day' in 52 % and limiting activities in the same proportion. Average pain score was 4.6 (SD 2.2; 0-10 scale). Age was associated with pain frequency and duration, with younger groups more often reporting pain 'some days' and 'dating back <3 months'. Results of regression analyses showed that individuals suffering from LBP had significantly more problems than LBP non-sufferers on all EQ-5D subscales, except self-care: pain/discomfort (OR 5.33; 95 % CI [4.19-6.79]), mobility (OR 2.66; 95 % CI [2.04-3.46]), usual activities (OR 1.92; 95 % CI [1.42-2.60]), anxiety/depression (OR 1.59; 95 % CI [1.23-2.04]) and self-care (OR 1.29; 95 % CI [0.84-1.98]).Conclusion: LBP appears to be a more permanent condition in the older groups. LBP may be a part of the definition of a subgroup of elderly at risk of becoming frail in relation with higher levels of functional limitations, psychological difficulties and social restrictions, hence globally impaired HRQoL. [ABSTRACT FROM AUTHOR]

Background: Despite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Recently, we found that the adaptive immune system is involved in the pathophysiology of chronic nociceptive and neuropathic pain in humans. So far, data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. We therefore analyzed the P2X7R expression on peripheral blood lymphocytes and monocytes, as well as serum levels of IL-1β in patients suffering from chronic nociceptive and neuropathic pain in comparison to healthy volunteers in order to identify individuals who might benefit from a P2X7R modulating therapy.Methods: P2X7R messenger RNA (mRNA) and protein expression were determined in patients with either chronic nociceptive low back pain (CLBP) or neuropathic pain (NeP), and in healthy volunteers by quantitative real-time PCR (qPCR) and by fluorescence-assisted cell-sorting (FACS), respectively. IL-1β serum levels were measured with a multiplex cytokine assay.Results: Compared to healthy volunteers, P2X7R mRNA (1.6-fold, p = 0.038) and protein levels were significantly increased on monocytes (NeP: 24.6 ± 6.2, healthy volunteers: 17.0 ± 5.4; p = 0.002) and lymphocytes (NeP: 21.8 ± 6.5, healthy volunteers: 15.6 ± 5.2; p = 0.009) of patients with NeP, but not in patients with CLBP. Similarly, IL-1β serum concentrations were significantly elevated only in NeP patients (1.4-fold, p = 0.04).Conclusions: A significant upregulation of P2X7R and increased IL-1β release seems to be a particular phenomenon in patients with NeP. P2X7R inhibitors may therefore represent a potential option for the treatment of this frequently intractable type of pain. German Clinical Trial Register (DRKS): Registration Trial DRKS00005954. [ABSTRACT FROM AUTHOR]

This work presents the poisoning effect of organic oxo-silicon compounds (siloxanes) which are generally found in sewage biogas. Lifetime and durability associated with solid oxide fuel cell (SOFC) technology is strongly related to the amount of contaminants that reach the stack. Several experiments on Ni anode-supported (AS) single cells are performed in order to clarify the mechanism of degradation and also the possibility of cell performance recovery. Three experiments focus on the degradation and recovery of AS Ni-YSZ fed with H2, co-feeding 5 ppm D4-siloxane (octamethylcyclotetrasiloxane, C8H24O4Si4) as representative compound for the organic silicon species, at 800 °C. A fourth experiment focuses on the durability of the AS Ni-YSZ cell with variable concentrations of the impurity (0-5 ppm), during steady state polarization (0.25 A cm−2) for 250 h, using simulated biogas-reformate fuel H2/CO/CO2/H2O: irreversible degradation was observed with the D4-impurity feed in the anode gas. Post-test scanning electron microscopy (SEM) results indicate formation of SiO2(s) deposits, which block pores and reduce the TPB length. [ABSTRACT FROM AUTHOR]

Background Penetrating injuries are rare in European populations so their management represents a particular challenge. The aim was to assess early therapeutic aspects that are associated with favourable outcomes in patients with penetrating trauma. Methods Patients with penetrating injuries documented from 2009 to 2013 in the TraumaRegister DGU® were analysed. Patients with a primary admission and an Injury Severity Score ( ISS) of at least 9 were included. The Revised Injury Severity Classification ( RISC) II score was used for mortality prediction, and a standardized mortality ratio ( SMR) calculated per hospital. Hospitals with favourable outcome ( SMR below 1) were compared with those with poor outcome ( SMR 1 or more). Results A total of 50 centres had favourable outcome (1242 patients; observed mortality rate 15·7 per cent) and 34 centres had poor outcome (918 patients; observed mortality rate 24·4 per cent). Predicted mortality rates according to RISC-II were 20·4 and 20·5 per cent respectively. Mean(s.d.) ISS values were 22(14) versus 21(14) ( P = 0·121). Patients in the favourable outcome group had a significantly shorter time before admission to hospital and a lower intubation rate. They received smaller quantities of intravenous fluids on admission to the emergency room, but larger amounts of fresh frozen plasma, and were more likely to receive haemostatic agents. A higher proportion of patients in the favourable outcome group were treated in a level I trauma centre. Independent risk factors for hospital death following penetrating trauma identified by multivariable analysis included gunshot injury mechanism and treatment in non-level I centres. Conclusion Among penetrating traumas, gunshot injuries pose an independent risk of death. Treatment of penetrating trauma in a level I trauma centre was significantly and independently associated with lower hospital mortality. [ABSTRACT FROM AUTHOR]