363 research outputs found

    Inhibition of retinoic acid signaling in proximal tubular epithelial cells protects against acute kidney injury

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    Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1. However, the protective effects of inhibiting PTEC RAR signaling were associated with increased Kim1-dependent apoptotic cell clearance, or efferocytosis, and this was associated with dedifferentiation, proliferation, and metabolic reprogramming of PTECs. These data demonstrate the functional role that reactivation of RAR signaling plays in regulating PTEC differentiation and function in human and experimental AKI

    No Evidence for Emotional Empathy in Chickens Observing Familiar Adult Conspecifics

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    The capacity of animals to empathise is of high potential relevance to the welfare of group-housed domestic animals. Emotional empathy is a multifaceted and multilayered phenomenon which ranges from relatively simple processes such as emotional matching behaviour to more complex processes involving interaction between emotional and cognitive perspective taking systems. Our previous research has demonstrated that hens show clear behavioural and physiological responses to the mild distress of their chicks. To investigate whether this capacity exists outside the mother/offspring bond, we conducted a similar experiment in which domestic hens were exposed to the mild distress of unrelated, but familiar adult conspecifics. Each observer hen was exposed to two replicates of four conditions, in counterbalanced order; control (C); control with noise of air puff (CN); air puff to conspecific hen (APC); air puff to observer hen (APH). During each test, the observer hens' behaviour and physiology were measured throughout a 10 min pre-treatment and a 10 min treatment period. Despite showing signs of distress in response to an aversive stimulus directed at themselves (APH), and using methodology sufficiently sensitive to detect empathy-like responses previously, observer hens showed no behavioural or physiological responses to the mild distress of a familiar adult conspecific. The lack of behavioural and physiological response indicates that hens show no basis for emotional empathy in this context

    The iCanCope pain self-management application for adolescents with juvenile idiopathic arthritis: A pilot randomized controlled trial

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    Objectives: To evaluate the feasibility and preliminary effectiveness of iCanCope with Pain (iCanCope), a smartphone-based pain self-management program, in adolescents with JIA. iCanCope featured symptom tracking, goal-setting, pain coping skills and social support. Methods: A two-arm pilot randomized controlled trial was used to evaluate the iCanCope app compared with a version with symptom tracking only. Primary (feasibility) outcomes were: participant accrual/attrition rates, success of app deployment, acceptability and adherence. Secondary (preliminary effectiveness) outcomes were: pain intensity, pain-related activity limitations and health-related quality of life. Outcomes were assessed at baseline and 8 weeks. Adherence was defined as the proportion of completed symptom reports: \u27low\u27 (≤24%); \u27low-moderate\u27 (25-49%); \u27high-moderate\u27 (50-75%); or \u27high\u27 (76-100%). Linear mixed models were applied for preliminary effectiveness analyses as per intention-to-treat. Results: Adolescents (N = 60) were recruited from three paediatric rheumatology centres. Rates of accrual and attrition were 82 and 13%, respectively. Both apps were deployed with high success (over 85%) and were rated as highly acceptable. Adherence was similar for both groups, with most participants demonstrating moderate-to-high adherence. Both groups exhibited a clinically meaningful reduction in pain intensity (≥1 point) that did not statistically differ between groups. There were no significant changes in activity limitations or health-related quality of life. Conclusion: The iCanCope pilot randomized controlled trial was feasible to implement in a paediatric rheumatology setting. Both apps were deployed successfully, with high acceptability, and were associated with moderate-to-high adherence. Preliminary reductions in pain intensity warrant a future trial to evaluate effectiveness of iCanCope in improving health outcomes in adolescents with JIA

    NSAID use and clinical outcomes in COVID-19 patients: a 38-center retrospective cohort study.

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    BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community-acquired pneumonia. Observations shortly after the start of the COVID-19 pandemic in 2020 suggested that ibuprofen was associated with an increased risk of adverse events in COVID-19 patients, but subsequent observational studies failed to demonstrate increased risk and in one case showed reduced risk associated with NSAID use. METHODS: A 38-center retrospective cohort study was performed that leveraged the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative. A propensity-matched cohort of 19,746 COVID-19 inpatients was constructed by matching cases (treated with NSAIDs at the time of admission) and 19,746 controls (not treated) from 857,061 patients with COVID-19 available for analysis. The primary outcome of interest was COVID-19 severity in hospitalized patients, which was classified as: moderate, severe, or mortality/hospice. Secondary outcomes were acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO), invasive ventilation, and all-cause mortality at any time following COVID-19 diagnosis. RESULTS: Logistic regression showed that NSAID use was not associated with increased COVID-19 severity (OR: 0.57 95% CI: 0.53-0.61). Analysis of secondary outcomes using logistic regression showed that NSAID use was not associated with increased risk of all-cause mortality (OR 0.51 95% CI: 0.47-0.56), invasive ventilation (OR: 0.59 95% CI: 0.55-0.64), AKI (OR: 0.67 95% CI: 0.63-0.72), or ECMO (OR: 0.51 95% CI: 0.36-0.7). In contrast, the odds ratios indicate reduced risk of these outcomes, but our quantitative bias analysis showed E-values of between 1.9 and 3.3 for these associations, indicating that comparatively weak or moderate confounder associations could explain away the observed associations. CONCLUSIONS: Study interpretation is limited by the observational design. Recording of NSAID use may have been incomplete. Our study demonstrates that NSAID use is not associated with increased COVID-19 severity, all-cause mortality, invasive ventilation, AKI, or ECMO in COVID-19 inpatients. A conservative interpretation in light of the quantitative bias analysis is that there is no evidence that NSAID use is associated with risk of increased severity or the other measured outcomes. Our results confirm and extend analogous findings in previous observational studies using a large cohort of patients drawn from 38 centers in a nationally representative multicenter database

    Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

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    Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

    Social odors conveying dominance and reproductive information induce rapid physiological and neuromolecular changes in a cichlid fish

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    Background: Social plasticity is a pervasive feature of animal behavior. Animals adjust the expression of their social behavior to the daily changes in social life and to transitions between life-history stages, and this ability has an impact in their Darwinian fitness. This behavioral plasticity may be achieved either by rewiring or by biochemically switching nodes of the neural network underlying social behavior in response to perceived social information. Independent of the proximate mechanisms, at the neuromolecular level social plasticity relies on the regulation of gene expression, such that different neurogenomic states emerge in response to different social stimuli and the switches between states are orchestrated by signaling pathways that interface the social environment and the genotype. Here, we test this hypothesis by characterizing the changes in the brain profile of gene expression in response to social odors in the Mozambique Tilapia, Oreochromis mossambicus. This species has a rich repertoire of social behaviors during which both visual and chemical information are conveyed to conspecifics. Specifically, dominant males increase their urination frequency during agonist encounters and during courtship to convey chemical information reflecting their dominance status. Results: We recorded electro-olfactograms to test the extent to which the olfactory epithelium can discriminate between olfactory information from dominant and subordinate males as well as from pre- and post-spawning females. We then performed a genome-scale gene expression analysis of the olfactory bulb and the olfactory cortex homolog in order to identify the neuromolecular systems involved in processing these social stimuli. Conclusions: Our results show that different olfactory stimuli from conspecifics' have a major impact in the brain transcriptome, with different chemical social cues eliciting specific patterns of gene expression in the brain. These results confirm the role of rapid changes in gene expression in the brain as a genomic mechanism underlying behavioral plasticity and reinforce the idea of an extensive transcriptional plasticity of cichlid genomes, especially in response to rapid changes in their social environment.Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [EXCL/BIA-ANM/0549/2012, Pest-OE/MAR/UI0331/2011]; Dwight W. and Blanche Faye Reeder Centennial Fellowship in Systematic and Evolutionary Biology; Institute for Cellular and Molecular Biology Fellowship; FCTinfo:eu-repo/semantics/publishedVersio

    Faster decline of pitch memory over time in congenital amusia

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    Congenital amusia (amusia, hereafter) is a developmental disorder that impacts negatively on the perception of music. Psychophysical testing suggests that individuals with amusia have above average thresholds for detection of pitch change and pitch direction discrimination; however, a low-level auditory perceptual problem cannot completely explain the disorder, since discrimination of melodies is also impaired when the constituent intervals are suprathreshold for perception. The aim of the present study was to test pitch memory as a function of (a) time and (b) tonal interference, in order to determine whether pitch traces are inherently weaker in amusic individuals. Memory for the pitch of single tones was compared using two versions of a paradigm developed by Deutsch (1970a). In both tasks, participants compared the pitch of a standard (S) versus a comparison (C) tone. In the time task, the S and C tones were presented, separated in time by 0, 1, 5, 10, and 15 s (blocked presentation). In the interference task, the S and C tones were presented with a fixed time interval (5 s) but with a variable number of irrelevant tones in between: 0, 2, 4, 6, and 8 tones (blocked presentation). In the time task, control performance remained high for all time in tervals, but amusics showed a performance decrement over time. In the interference task, controls and amusics showed a similar performance decrement with increasing number of irrelevant tones. Overall, the results suggest that the pitch representations of amusic individuals are less stable and more prone to decay than those of matched non-amusic individuals
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