Autophagy Inhibition in Pain: Role of a microRNA

Neuropathic pain caused by peripheral nerve injury (PNI) leads to the activation and infiltration of microglial cells and to a neuroinflammatory-induced pain state. miRNAs and autophagy are two main factors and/or mechanisms which have the ability to alter the pain state. In this study, miR-195 was shown to be markedly increased after PNI and associated with the pain phenotype. In addition, inhibition of autophagy in vivo led to p62 accumulation, decreased production of LC3, and inhibition of ATG14

A Universal Property of Axonal and Dendritic Arbors

SummaryAxonal and dendritic arbors can be characterized statistically by their spatial density function, a function that specifies the probability of finding a branch of a particular arbor at each point in a neural circuit. Based on an analysis of over a thousand arbors from many neuron types in various species, we have discovered an unexpected simplicity in arbor structure: all of the arbors we have examined, both axonal and dendritic, can be described by a Gaussian density function truncated at about two standard deviations. Because all arbors are characterized by density functions with this single functional form, only four parameters are required to specify an arbor's size and shape: the total length of its branches and the standard deviations of the Gaussian in three orthogonal directions. This simplicity in arbor structure can have implications for the developmental wiring of neural circuits

Port Townsend liquids depot: environmental impact assessment of a biofuels facility on the Port Townsend Paper Corporation site

This Environmental Impact Assessment (EIA) has been compiled in accordance to the Washington State Environmental Protection Act (SEPA). Its purpose is to analyze and determine the environmental, social, and economic impacts of co-locating a liquid depot facility at the pre-existing Port Townsend Paper Corporation. The Northwest Advanced Renewables Alliance (NARA) has proposed the project, which is siting a liquids depot on land owned by the PTPC. This EIA will analyze all potential significant impacts produced by the proposal and consider all elements as outlined by SEPA

Differential Expression of RNA in the Rat Peripheral Nervous System Following Nerve Injury and Treatment with Pain-Relieving Celecoxib-Loaded Nanomedicine

The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the expression profiles of RNAs in neurons, glia and infiltrating immune cells: a neuro-immune triad. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Macrophages that phagocytose intravenously injected nanoemulsion carrying the non-steroidal anti-inflammatory, NSAID, Celecoxib, naturally accumulate at the site of injury resulting in relief of CCI behavioral hyper-sensitivity. It is not known beyond the inhibition of cyclooxygenase-2 (COX-2) activity and the reduction in prostaglandin E2 (PGE2), what gene expression may be altered by this treatment. Previously, we showed that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduced inflammation of the sciatic nerve and relieved pain-like behavior for up to 6 days. To elucidate aspects of the molecular mechanisms underlying CCI pain as well as pain relief, I assessed an NSAID-loaded nanoemulsion macrophage-targeted therapy to explore changes in RNA expression in both pain and pain-relieved states. Sciatic nerve and dorsal root ganglia (DRG) tissue from CCI animals was used to evaluate the expression profiles utilizing quantitative polymerase chain reactions (qPCR) and RNA sequencing, respectively. In the injured sciatic nerve treated with drug-loaded nanoemulsion, I observed mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine mRNA expression. Furthermore, genes associated with selective adhesion of macrophages, as well as changes in the neuronal and glial associated mRNAs were observed. Moreover, several neuroactive genes were found to respond to the celecoxib loaded nanoemulsion in animals receiving pain relief as compared to animals that received drug-free vehicle including: Monoamine oxidase B (MAOB), NMDA-Receptor 2b (Grin2b), Calcium channel TRPV3, Interleukin IL-6, Voltage-dependent Calcium channel subunit alpha 1B (Cacna1b/C2v2.2), Integrin alpha M (Itgam/Cd11b), Sodium channel Nav1.7 (Scn9a), and Preprotachykinin-1 (Tac1), which produces neurokinin A and substance P. The transcriptome of the ipsilateral DRGs was assessed using high throughput RNA sequencing to provide insight into the molecular mechanisms involved in the underlying neuroimmune response. Comparing the DRG transcriptome of CCI animals treated with celecoxib-loaded nanoemulsion (CXB-NE) as well as drug-free (vehicle) nanoemulsion (DF-NE) to naïve, unoperated rats revealed significant differential RNA expression of 115 genes. Differential expression of particular transcripts was validated by quantitative PCR in the DRG and the bioinformatics tool PANTHER (protein annotation through evolutionary relationship) revealed that the differentially expressed genes involved in the neuroinflammatory response are associated with several key signaling mechanisms. This study showed that by directly inhibiting COX-2 activity in infiltrating macrophages at the site of injury on the sciatic nerve, there was a subsequent change in RNA expression in cell bodies of the DRG. While it is not surprising that peripheral nerve injury is associated with extensive changes in the expression profile of RNAs in the associated DRG, it is clear that attenuating the activity of COX-2 and the corresponding reduction in PGE2 at the site of injury results in changes in the transcriptome of the associated DRG reflecting pain relief as well as the partial reversal of the gene expression profiles in the injured sciatic nerve associated with chronic pain. Overall, it can be concluded that by solely targeting COX-2 production in macrophages in the CCI model, there is a direct effect of gene expression changes related to cells associated with the neuroimmune triad, the axon regeneration process, and the chronic pain response

Reducing the within-patient variability of breathing for radiotherapy delivery in conscious, unsedated cancer patients using a mechanical ventilator

OBJECTIVE: Variability in the breathing pattern of patients with cancer during radiotherapy requires mitigation, including enlargement of the planned treatment field, treatment gating and breathing guidance interventions. Here, we provide the first demonstration of how easy it is to mechanically ventilate patients with breast cancer while fully conscious and without sedation, and we quantify the resulting reduction in the variability of breathing. METHODS: 15 patients were trained for mechanical ventilation. Breathing was measured and the left breast anteroposterior displacement was measured using an Osiris surface-image mapping system (Qados Ltd, Sandhurst, UK). RESULTS: Mechanical ventilation significantly reduced the within-breath variability of breathing frequency by 85% (p < 0.0001) and that of inflation volume by 29% (p < 0.006) when compared with their spontaneous breathing pattern. During mechanical ventilation, the mean amplitude of the left breast marker displacement was 5 ± 1 mm, the mean variability in its peak inflation position was 0.5 ± 0.1 mm and that in its trough inflation position was 0.4 ± 0.0 mm. Their mean drifts were not significantly different from 0 mm min(−1) (peak drift was −0.1 ± 0.2 mm min(−1) and trough drift was −0.3 ± 0.2 mm min(−1)). Patients had a normal resting mean systolic blood pressure (131 ± 5 mmHg) and mean heart rate [75 ± 2 beats per minute (bpm)] before mechanical ventilation. During mechanical ventilation, the mean blood pressure did not change significantly, mean heart rate fell by 2 bpm (p < 0.05) with pre-oxygenation and rose by only 4 bpm (p < 0.05) during pre-oxygenation with hypocapnia. No patients reported discomfort and all 15 patients were always willing to return to the laboratory on multiple occasions to continue the study. CONCLUSION: This simple technique for regularizing breathing may have important applications in radiotherapy. ADVANCES IN KNOWLEDGE: Variations in the breathing pattern introduce major problems in imaging and radiotherapy planning and delivery and are currently addressed to only a limited extent by asking patients to breathe to auditory or visual guidelines. We provide the first demonstration that a completely different technique, of using a mechanical ventilator to take over the patients' breathing for them, is easy for patients who are conscious and unsedated and reduces the within-patient variability of breathing. This technique has potential advantages in radiotherapy over currently used breathing guidance interventions because it does not require any active participation from or feedback to the patient and is therefore worthy of further clinical evaluation

Adding Fizz to Your Science Classroom

Have you found that your science classes just skip from unit to unit? Do you want to get away from science lessons that stress vocabulary and memorization of facts? Are you pondering how to get your students more involved in science? These were some of the questions we thought about when we designed hands-on experiences in science for upper elementary students. According to the National Research Council in Fulfilling the Promise, Biology Education in the Nation\u27s Schools, future curriculum goals for both elementary and secondary science teaching will emphasize hands-on exploration by the students, the development of skills in observation, comparison, measurement, questioning and understanding and the view of science education as a continuous, interrelated process rather than isolated units of study

Septic-associated encephalopathy - everything starts at a microlevel

Sepsis-associated encephalopathy is associated with increased mortality and morbidity. Its pathophysiology remains insufficiently elucidated, although there is evidence for a neuroinflammatory process sequentially involving endothelial activation, blood-brain barrier alteration and cellular dysfunction and alteration in neurotransmission. Experimental studies have shown that microcirculatory dysfunction, a consequence of endothelial activation, is an early pathogenic step. To date, we do not know whether it is present in septic patients, whether it accounts for clinical features and whether it is treatable

Pyrophytic Tree Classification in Berea Forest using Unmanned Aerial Systems

Pyrophyte - Tree species adapted to endure fire. Despite its defenses, -Passive Pyrophyte - Resist the effects of fire. -Active Pyrophyte - Requires fire to spread, germinate, and regrow Despite its defenses, a pyrophyte can be overwhelmed and destroyed by fire. After decades of total fire suppression policies along with rising average temperatures as a result of climate change, forest fires have grown in intensity, frequency, and coverage. With the assistance of Unmanned Aerial Systems (UAS), foresters can survey the distribution of pyrophytic trees and develop sustainable approaches to forest management that restore the natural ecosystem and reduce the threat of forest fires