The mode of action of IL-23 in experimental inflammatory arthritic pain and disease.

Objectives: We have previously reported using gene-deficient mice that the interleukin (IL)-23p19 subunit is required for the development of innate immune-driven arthritic pain and disease. We aimed to explore here, using a number of in vivo approaches, how the IL-23p19 subunit can mechanistically control arthritic pain and disease in a T- and B- lymphocyte-independent manner.

Methods: We used the zymosan-induced arthritis (ZIA) model in wild-type and Il23p19 mice, by a radiation chimera approach, and by single cell RNAseq and qPCR analyses, to identify the IL23p19-expressing and IL-23-responding cell type(s) in the inflamed joints.

IL-23 regulation of myeloid cell biology during inflammation.

Interleukin (IL)-23 is implicated in the pathogenesis of several inflammatory diseases and is usually linked with helper T cell (Th17) biology. However, there is some data linking IL-23 with innate immune biology in such diseases. We therefore examined the effects of IL-23p19 genetic deletion and/or neutralization on in vitro macrophage activation and in an innate immune-driven peritonitis model.

An immuno-epidemiological model for transient immune protection: A case study for viral respiratory infections.

The dynamics of infectious disease in a population critically involves both within-host pathogen replication and between host pathogen transmission. While modeling efforts have recently explored how within-host dynamics contribute to shaping population transmission, fewer have explored how ongoing circulation of an epidemic infectious disease can impact within-host immunological dynamics. We present a simple, influenza-inspired model that explores the potential for re-exposure during a single, ongoing outbreak to shape individual immune response and epidemiological potential in non-trivial ways.

Call of the wild: creating a formal wilderness medicine elective for Canadian pre-clerkship medical students.

Wilderness medicine education is interesting to medical students, yet not widely implemented in Canadian medical curricula. We describe a curriculum for a pre-clerkship wilderness medicine elective at a Canadian medical school. Our study reports increased student awareness of career opportunities in wilderness medicine after elective completion, and interest in hands-on learning for wilderness medicine topics.

Nitrogen-Induced Hysteresis in Grassland Biodiversity: A Theoretical Test of Litter-Mediated Mechanisms.

AbstractThe global rise in anthropogenic reactive nitrogen and the negative impacts of N deposition on terrestrial plant diversity are well documented. The R* theory of resource competition predicts reversible decreases in plant diversity in response to N loading. However, empirical evidence for the reversibility of N-induced biodiversity loss is mixed.

Task-Evoked Pupillary Response as a Potential Biomarker of Dementia and Mild Cognitive Impairment: A Scoping Review.

Pupil dilation functions as a proxy for cognitive effort and can be measured through automated pupillometry. The aim of this scoping review is to examine how individuals with cognitive impairment differ in task-evoked pupillary responses relative to cognitively healthy individuals. A systematic literature search across six databases was conducted to identify studies examining changes in pupillary responses evoked by cognitive tasks comparing patients with dementia to healthy controls.

Assessing the binding interaction of polystyrene sulfonate with amitriptyline in healthy volunteers: a cross-over design - The BIND study.

Purpose: Polystyrene sulfonate is used for binding potassium in patients with chronic kidney disease (CKD). Because of its binding properties, it can potentially bind other medications and thereby decrease their bioavailability and effectiveness. Amitriptyline, often used by CKD patients for neuropathic pain, shows significant binding to polystyrene sulfonate in vitro.

Effects of stochasticity on the length and behaviour of ecological transients.

There is a growing recognition that ecological systems can spend extended periods of time far away from an asymptotic state, and that ecological understanding will therefore require a deeper appreciation for how long ecological transients arise. Recent work has defined classes of deterministic mechanisms that can lead to long transients. Given the ubiquity of stochasticity in ecological systems, a similar systematic treatment of transients that includes the influence of stochasticity is important.

Role of N-methyl-d-aspartate receptor subunits GluN2A and GluN2B in auditory thalamocortical long-term potentiation in adult mice.

Cortical neurons undergo continuous remodelling throughout development and into adulthood, associated with long-term changes in the synaptic transmission of thalamocortical pathways, i.e., long-term potentiation (LTP); such plasticity is input-specific, reflected in the frequency-specificity of the auditory system.

Effects of Transcranial Direct Current Stimulation (tDCS) on Cognitive Performance and Cerebral Oxygen Hemodynamics: A Systematic Review.

There is increasing evidence to support the efficacy of transcranial direct current stimulation (tDCS) applications in cognitive augmentation and rehabilitation. Neuromodulation achieved with tDCS may further regulate regional cerebral perfusion affiliated through the neurovascular unit; however, components of cerebral perfusion decrease across aging. A novel neuroimaging approach, functional near-infrared spectroscopy (fNIRS), can aid in quantifying these regional perfusional changes.

Management implications of long transients in ecological systems.

The underlying biological processes that govern many ecological systems can create very long periods of transient dynamics. It is often difficult or impossible to distinguish this transient behaviour from similar dynamics that would persist indefinitely. In some cases, a shift from the transient to the long-term, stable dynamics may occur in the absence of any exogenous forces.

Altered energy partitioning across terrestrial ecosystems in the European drought year 2018.

Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands).

Human chimeric antigen receptor macrophages for cancer immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging. Given the unique effector functions of macrophages and their capacity to penetrate tumors, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype.

Optimising the dose of clonidine to achieve sedation in intensive care unit patients with population pharmacokinetics.

Aims: The aim of this study was to investigate the population pharmacokinetics (PK) of clonidine in intensive care unit (ICU) patients in order to develop a dosing regimen for sedation.

Methods: We included 24 adult mechanically ventilated, sedated patients from a mixed medical and surgical ICU. Intravenous clonidine was added to standard sedation in doses of 600, 1200 or 1800 μg/d.

Long transients in ecology: Theory and applications.

This paper discusses the recent progress in understanding the properties of transient dynamics in complex ecological systems. Predicting long-term trends as well as sudden changes and regime shifts in ecosystems dynamics is a major issue for ecology as such changes often result in population collapse and extinctions. Analysis of population dynamics has traditionally been focused on their long-term, asymptotic behavior whilst largely disregarding the effect of transients.

In vivo Elimination of Clonidine by Continuous Venovenous Hemofiltration in Critically Ill Patients.

Background: Clonidine is an α2-agonist that is commonly used for sedation in the intensive care unit. When patients are on continuous venovenous hemofiltration (CVVH) in the presence of kidney dysfunction, the sieving coefficient of clonidine is required to estimate how much drug is removed by CVVH. In the present study, we measured the sieving coefficient of clonidine in critically ill, ventilated patients receiving CVVH.

On the calculation of daytime CO fluxes measured by automated closed transparent chambers.

Automated transparent chambers have gained increasing popularity in recent years to continuously measure net CO fluxes between low-statured canopies and the atmosphere. In this study, we carried out four field campaigns with chamber measurements in a variety of mountainous grasslands. A mathematic stationary point (or critical point, a point at which the derivative of a function is zero) in the CO mixing ratio time series was found in a substantial fraction of the measurements at all the sites, which had a significant influence on the performances of the regression algorithms.

Pain After Whole-Body Vibration Exposure Is Frequency Dependent and Independent of the Resonant Frequency: Lessons From an In Vivo Rat Model.

Occupational whole-body vibration (WBV) increases the risk of developing low back and neck pain; yet, there has also been an increased use of therapeutic WBV in recent years. Although the resonant frequency (fr) of the spine decreases as the exposure acceleration increases, effects of varying the vibration profile, including peak-to-peak displacement (sptp), root-mean-squared acceleration (arms), and frequency (f), on pain onset are not known. An established in vivo rat model of WBV was used to characterize the resonance of the spine using sinusoidal sweeps.

[A vulnerable elderly man with prednisone-induced delirium].

A vulnerable elderly man with prednisone-induced delirium Background Delirium always has an underlying cause, for example, medication. This article describes the case of a man with severe delirium caused by prednisone. Case description A 91-year-old vulnerable man developed severe delirium with agitation, verbal and physical aggression and visual hallucinations 3 days after starting treatment with low-dose prednisone.

Estimation of evapotranspiration of temperate grassland based on high-resolution thermal and visible range imagery from unmanned aerial systems.

Spatially distributed high-resolution data of land surface temperature (LST) and evapotranspiration (ET) are important information for crop water management and other applications in the agricultural sector. While satellite data can provide LST high-resolution data of 100 m, the current development of unmanned aerial systems (UAS) and affordable low-weight thermal cameras allows LST and subsequent ET to be derived at resolutions down to centimetre scale. In this study, UAS-based images in the thermal infrared (TIR) and visible spectral range were collected over a managed temperate grassland in July 2016 at the Terrestrial Environmental Observatories Networks TERENO preAlpine observatory site at Fendt, Germany.

Transient phenomena in ecology.

The importance of transient dynamics in ecological systems and in the models that describe them has become increasingly recognized. However, previous work has typically treated each instance of these dynamics separately. We review both empirical examples and model systems, and outline a classification of transient dynamics based on ideas and concepts from dynamical systems theory.

Greenhouse gas fluxes over managed grasslands in Central Europe.

Central European grasslands are characterized by a wide range of different management practices in close geographical proximity. Site-specific management strategies strongly affect the biosphere-atmosphere exchange of the three greenhouse gases (GHG) carbon dioxide (CO ), nitrous oxide (N O), and methane (CH ). The evaluation of environmental impacts at site level is challenging, because most in situ measurements focus on the quantification of CO exchange, while long-term N O and CH flux measurements at ecosystem scale remain scarce.

Cortical frequency-specific plasticity is independently induced by intracortical circuitry.

Auditory learning induces frequency-specific plasticity in the auditory cortex. Both the auditory cortex and thalamus are involved in the cortical plasticity; however, the precise role of the intracortical circuity remains unclear until the contributions of the thalamocortical inputs are controlled. Here, we induced cortical plasticity by local activation of the primary auditory cortex (AI) via intracortical electrical stimulation (ES) in C57 mice and found a similar pattern of cortical plasticity was induced by ES when the auditory thalamus was inactivated or remained active during the ES.

The nuclear transport receptor Importin-11 is a tumor suppressor that maintains PTEN protein.

Phosphatase and tensin homologue (PTEN) protein levels are critical for tumor suppression. However, the search for a recurrent cancer-associated gene alteration that causes PTEN degradation has remained futile. In this study, we show that Importin-11 (Ipo11) is a transport receptor for PTEN that is required to physically separate PTEN from elements of the PTEN degradation machinery.