Distinct Molecular Processes Mediate Donor-derived Cell-free DNA Release From Kidney Transplants in Different Disease States.

Background: Among all biopsies in the Trifecta-Kidney Study ( ClinicalTrials.gov NCT04239703), elevated plasma donor-derived cell-free DNA (dd-cfDNA) correlated most strongly with molecular antibody-mediated rejection (AMR) but was also elevated in other states: T cell-mediated rejection (TCMR), acute kidney injury (AKI), and some apparently normal biopsies. The present study aimed to define the molecular correlates of plasma dd-cfDNA within specific states.

Environmental risk of nickel in aquatic Arctic ecosystems.

The Arctic faces many environmental challenges, including the continued exploitation of its mineral resources such as nickel (Ni). The responsible development of Ni mining in the Arctic requires establishing a risk assessment framework that accounts for the specificities of this unique region. We set out to conduct preliminary assessments of Ni exposure and effects in aquatic Arctic ecosystems.

Mechanism of copper nanoparticle toxicity in rainbow trout olfactory mucosa.

Chemosensory perception is crucial for fish reproduction and survival. Direct contact of olfactory neuroepithelium to the surrounding environment makes it vulnerable to contaminants in aquatic ecosystems. Copper nanoparticles (CuNPs), which are increasingly used in commercial and domestic applications due their exceptional properties, can impair fish olfactory function.

Vape flavourants dull sensory perception and cause hyperactivity in developing zebrafish embryos.

E-cigarette use (vaping) during pregnancy has been increasing, and the potential exists for the developing brain to be exposed to chemical constituents in the vape. Vapes come in over 7000 unique flavours with and without nicotine, and while nicotine is a known neurotoxicant, the effects of vape flavouring alone, in the absence of nicotine, on brain function are not well understood. Here, we performed a screen of vape aerosol extracts (VAEs) to determine the potential for prenatal neurotoxicity using the zebrafish embryo photomotor response (PMR)-a translational biosensor of neurobehavioural effects.

Municipal wastewater effluent exposure disrupts early development, larval behavior, and stress response in zebrafish.

While wastewater treatment standards have been progressively increasing, emerging contaminants such as pharmaceuticals can nonetheless pass through treatment and end up in our watersheds. Pharmaceuticals in the parts-per-billion range can impact fish behavior, survival, and recruitment in the wild. However, the ecological risk posed by whole municipal wastewater effluents (MWWE), a complex mixture, is not clear.

A rapid zebrafish embryo behavioral biosensor that is capable of detecting environmental β-blockers.

β-Blockers (BB) are one of the most commonly prescribed pharmaceuticals used for treating cardiovascular and acute anxiety-related disorders. This class of drugs inhibit β-adrenoceptor signalling and given their growing, widespread use, BB are routinely detected in surface waters at nM concentrations. This is concerning as trace levels of BB impart developmental and reproductive dysfunction in non-target aquatic organisms, with potential for ecological risks.

Nonlinear mixed-modelling discriminates the effect of chemicals and their mixtures on zebrafish behavior.

Zebrafish (Danio rerio) early-life stage behavior has the potential for high-throughput screening of neurotoxic environmental contaminants. However, zebrafish embryo and larval behavioral assessments typically utilize linear analyses of mean activity that may not capture the complexity of the behavioral response. Here we tested the hypothesis that nonlinear mixed-modelling of zebrafish embryo and larval behavior provides a better assessment of the impact of chemicals and their mixtures.

Grafts of Olfactory Stem Cells Restore Breathing and Motor Functions after Rat Spinal Cord Injury.

The transplantation of olfactory ecto-mesenchymal stem cells (OEMSCs) could be a helpful therapeutic strategy for spinal cord repair. Using an acute rat model of high cervical contusion that provokes a persistent hemidiaphragmatic and foreleg paralysis, we evaluated the therapeutic effect of a delayed syngeneic transplantation (two days post-contusion) of OEMSCs within the injured spinal cord. Respiratory function was assessed using diaphragmatic electromyography and neuroelectrophysiological recordings of phrenic nerves (innervating the diaphragm).

Lifelong Exposure to PCBs in the Remote Norwegian Arctic Disrupts the Plasma Stress Metabolome in Arctic Charr.

Lake Ellasjøen on the remote Norwegian island of Bjørnøya is populated by Arctic charr (Salvelinus alpinus) having 20-fold higher body burdens of polychlorinated biphenyls (PCB) compared to charr from the neighboring Lake Laksvatn. This provides a natural setting to test the hypothesis that lifelong exposure to PCBs compromises the energy metabolism in this northernmost living salmonid. To test this, blood was sampled from charr from both lakes immediately after capture and following a 1 h handling and confinement stressor to assess possible differences in their energy metabolism and energy substrate mobilization, respectively.

Interactive toxicity of Ni, Zn, Cu, and Cd on Daphnia magna at lethal and sub-lethal concentrations.

The toxicity of metal mixtures is currently of particular interest among aquatic toxicologists. To provide insight into whether the interaction of multiple metals is similar at different biological levels, the survival and feeding behavior of Daphnia magna were studied following exposure to four metals (Cd, Cu, Ni, Zn) and their binary and quaternary combinations. In terms of survival, Zn-Cu and Cu-Cd mixtures produced more-than-additive mortality, while Ni-Cd mixtures resulted in less-than-additive mortality.

Testing Local Adaptation in Five Populations of Hyalella azteca in Northern Alberta's Oil Sands Region.

Canada's oil sands hold the third largest petroleum reserves worldwide and have experienced rapid economic growth. The oil sands region provides an ideal location for studying local adaptations through reciprocal transplant (RT) because populations within the region have been historically exposed to naturally occurring bitumen. Our objectives were to (1) determine if Hyalella azteca from habitats within the oil sands region exhibited increased tolerance to constituents associated with industrial bitumen extraction compared with H.

Organizing Publicly Funded Substance Use Disorder Treatment in the United States: Moving Toward a Service System Approach.

Historically, publicly funded substance use disorder (SUD) treatment services in the United States have been disorganized and inefficient. By reconfiguring and linking services to create systems of care-services, structures, and processes that are purposively interconnected to treat SUD systematically-health systems can transform discrete service components into cohesive service systems that comprehensively and efficiently treat SUDs. In this article we: (1) articulate the potential benefits of organizing publicly funded SUD services into systems of care; (2) review basic principles underlying theories of SUD system organization; (3) describe the mix and configuration of services needed to create comprehensive, integrated systems of publicly funded SUD care; (4) elucidate how patients can flow through systems of SUD services in a clinically sound and cost-efficient manner, and; (5) propose eight steps that can be taken to create systems of care by identifying and leveraging the strengths, assets, and capacities of SUD service providers already operating within their health care systems.

Behavioural alterations from exposure to Cu, phenanthrene, and Cu-phenanthrene mixtures: linking behaviour to acute toxic mechanisms in the aquatic amphipod, Hyalella azteca.

Phenanthrene (PHE) and Cu are two contaminants commonly co-occurring in marine and freshwater environments. Mixtures of PHE and Cu have been reported to induce more-than-additive lethality in the amphipod, Hyalella azteca, a keystone aquatic invertebrate, yet little is understood regarding the interactive toxic mechanisms that mediate more-than-additive toxicity. Understanding the interactions among toxic mechanisms among Cu and PHE will allow for better predictive power in assessing the ecological risks of Cu-PHE mixtures in aquatic environments.

Metal-Polycyclic Aromatic Hydrocarbon Mixture Toxicity in Hyalella azteca. 1. Response Surfaces and Isoboles To Measure Non-additive Mixture Toxicity and Ecological Risk.

Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) occur ubiquitously in aquatic environments, yet relatively little is known regarding their potential to produce non-additive toxicity (i.e., antagonism or potentiation).

Metal-Polycyclic Aromatic Hydrocarbon Mixture Toxicity in Hyalella azteca. 2. Metal Accumulation and Oxidative Stress as Interactive Co-toxic Mechanisms.

Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) are commonly found in aquatic environments. Emerging reports have identified that more-than-additive mortality is common in metal-PAH mixtures. Individual aspects of PAH toxicity suggest they may alter the accumulation of metals and enhance metal-derived reactive oxygen species (ROS).

Metal-PAH mixtures in the aquatic environment: a review of co-toxic mechanisms leading to more-than-additive outcomes.

Mixtures of metals and polycyclic aromatic hydrocarbons (PAHs) occur ubiquitously in aquatic environments, yet relatively little is known regarding their combined toxicities. Emerging reports investigating the additive mortality in metal-PAH mixtures have indicated that more-than-additive effects are equally as common as strictly-additive effects, raising concern for ecological risk assessment typically based on the summation of individual toxicities. Moreover, the current separation of focus between in vivo and in vitro studies, and fine- and coarse-scale endpoints, creates uncertainty regarding the mechanisms of co-toxicity involved in more-than-additive effects on whole organisms.

Extensive respiratory plasticity after cervical spinal cord injury in rats: axonal sprouting and rerouting of ventrolateral bulbospinal pathways.

Spinal cord injury (SCI) causes an interruption of descending motor and autonomic nervous tracts. However, a partial injury, and particularly a unilateral section, is generally followed by spontaneous locomotor and respiratory recovery. Although locomotor functional recovery has been correlated to spontaneous anatomical plasticity of the corticospinal tract, the remodeling of the bulbospinal tract that sustains respiratory improvement is unknown and has therefore been investigated here after chronic lateral cervical injury in rats (90 days post-lesion by comparison to 7 days post-lesion).

Alteration of forebrain neurogenesis after cervical spinal cord injury in the adult rat.

Spinal cord injury (SCI) triggers a complex cellular response at the injury site, leading to the formation of a dense scar tissue. Despite this local tissue remodeling, the consequences of SCI at the cellular level in distant rostral sites (i.e.

Effect of cervical spinal cord hemisection on the expression of axon growth markers.

To evaluate the plasticity processes occurring in the spared and injured tissue after partial spinal cord injury, we have compared the level of axon growth markers after a C2 cervical hemisection in rats between the contralateral (spared) and ipsilateral (injured) cervical cord using western blotting and immunohistochemical techniques. In the ipsilateral spinal cord 7 days after injury, although GAP-43 levels were increased in the ventral horn caudal to the injury, they were globally decreased in the whole structure (C1-C6). By contrast, in the contralateral intact side 7 days and 1 month after injury, we have found an increase of GAP-43 and betaIII tubulin levels, suggesting that processes of axonal sprouting may occur in the spinal region contralateral to the injury.

Are rodents an appropriate pre-clinical model for treating spinal cord injury? Examples from the respiratory system.

Because most studies of the effects of spinal cord injury (SCI) and resulting repair and treatments use rodent models, it is important to determine if these models are relevant to humans. In this review, we focus on alterations in respiratory function as a result of SCI. Several injury paradigms have been used in the rat to examine restoration of post-lesion respiratory function and potential benefits from repair strategies designed for humans.

Long-term reorganization of respiratory pathways after partial cervical spinal cord injury.

High cervical spinal cord injury (SCI) interrupts bulbospinal respiratory pathways innervating phrenic motoneurons, and induces an inactivation of phrenic nerves (PN) and diaphragm. We have previously shown that the ipsilateral (ipsi) PN was inactivated following a lateral C2 SCI, but was spontaneously partially reactivated 7 days post-SCI. This phrenic reactivation depended on contralateral (contra) descending pathways, located laterally, that cross the spinal midline.