ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity.

Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction.

Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation of stimulator of interferon response cGAMP interactor 1 (STING) signaling is pivotal for type I IFN induction. We hypothesized that vinorelbine, a chemotherapeutic and activator of STING, would cause a neuropathic pain-like state in mice via STING signaling in DRG neurons associated with IFN production.

Highly specific σR/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response.

The sigma 2 receptor (σR) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σR/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal antinociceptive effect is approximately 24 h following dosing. We sought to understand this unique antineuropathic pain effect by addressing two key questions: do these σR/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout mice for we find that a σR/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce antinociception in the spared nerve injury model in mice.

Vinorelbine causes a neuropathic pain-like state in mice via STING and MNK1 signaling associated with type I interferon induction.

Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization in mice. Activation of STING signaling is a key component of type I IFN induction. Manipulation of STING signaling is an active area of investigation in cancer and other therapeutic areas.

Highly specific σR/TMEM97 ligand alleviates neuropathic pain and inhibits the integrated stress response.

The Sigma 2 receptor (σR) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σR/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal anti-nociceptive effect is approximately 24 hours following dosing. We sought to understand this unique anti-neuropathic pain effect by addressing two key questions: do these σR/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout (KO) mice for we find that a new σR/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce anti-nociception in the spared nerve injury model in mice.

Mechanism of nanoplastics capture by jellyfish mucin and its potential as a sustainable water treatment technology.

The accumulation of nanoplastics (NPs) in the environment has raised concerns about their impact on human health and the biosphere. The main aim of this study is to understand the mechanism that governs the capture of NPs by jellyfish mucus extracted from the jellyfish Aurelia sp. (A.

A Female-Specific Role for Calcitonin Gene-Related Peptide (CGRP) in Rodent Pain Models.

We aimed to investigate a sexually dimorphic role of calcitonin gene-related peptide (CGRP) in rodent models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 signaling, CGRP receptor antagonists olcegepant and CGRP both given intrathecally, blocked, and reversed hyperalgesic priming only in females.

Influence of Graphene Nanoplatelet Lateral Size on the Electrical Conductivity and Electromagnetic Interference Shielding Performance of Polyester Nanocomposites.

Polyester nanocomposites reinforced with graphene nanoplatelets (GnPs) with two different lateral sizes are prepared by high shear mixing, followed by compression molding. The effects of the size and concentration of GnP, as well as of the processing method, on the electrical conductivity and electromagnetic interference (EMI) shielding behavior of these nanocomposites are experimentally investigated. The in-plane electrical conductivity of the nanocomposites with larger-size GnPs is approximately one order of magnitude higher than the cross-plane volume conductivity.

Ultra-Low Percolation Threshold Induced by Thermal Treatments in Co-Continuous Blend-Based PP/PS/MWCNTs Nanocomposites.

The effect of the crystallization of polypropylene (PP) forming an immiscible polymer blend with polystyrene (PS) containing conductive multi-wall carbon nanotubes (MWCNTs) on its electrical conductivity and electrical percolation threshold (PT) was investigated in this work. PP/PS/MWCNTs composites with a co-continuous morphology and a concentration of MWCNTs ranging from 0 to 2 wt.% were obtained.

A ligand-receptor interactome platform for discovery of pain mechanisms and therapeutic targets.

In the peripheral nervous system, ligand-receptor interactions between cells and neurons shape sensory experience, including pain. We set out to identify the potential interactions between sensory neurons and peripheral cell types implicated in disease-associated pain. Using mouse and human RNA sequencing datasets and computational analysis, we created interactome maps between dorsal root ganglion (DRG) sensory neurons and an array of normal cell types, as well as colitis-associated glial cells, rheumatoid arthritis-associated synovial macrophages, and pancreatic tumor tissue.

Review of Technologies and Materials Used in High-Voltage Film Capacitors.

High-voltage capacitors are key components for circuit breakers and monitoring and protection devices, and are important elements used to improve the efficiency and reliability of the grid. Different technologies are used in high-voltage capacitor manufacturing process, and at all stages of this process polymeric films must be used, along with an encapsulating material, which can be either liquid, solid or gaseous. These materials play major roles in the lifespan and reliability of components.

Development of Reinforced Polyester/Graphene Nanocomposite Showing Tailored Electrical Conductivity.

Production process was chosen in order to be readily scalable at the industrial level. The resin/graphene mixture was prepared through high shear mixing at six different weight concentrations between 0% and 10%. Samples were subsequently produced by compression molding.

Microplastic distributions in a domestic wastewater treatment plant: Removal efficiency, seasonal variation and influence of sampling technique.

Wastewater treatment plants (WWTPs) serve as an important route of microplastics (MPs) to the environment. Therefore, more effective MPs sampling and detection methodologies, as well as a better understanding of their influence on MPs occurrence and distributions in WWTP effluents, are needed for better removal and control. In this work, the efficiency of a municipal WWTP to remove MPs was assessed by collecting samples from raw to tertiary effluent during a 12-month sampling campaign (season-based) using different sampling methods (containers, 24-h composite and large grab samples).

Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis.

Background & Aims: We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration.

Methods: In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines).

Between source and sea: The role of wastewater treatment in reducing marine microplastics.

Wastewater treatment plants (WWTPs) are a focal point for the removal of microplastic (MP) particles before they are discharged into aquatic environments. WWTPs are capable of removing substantial quantities of larger MP particles but are inefficient in removing particles with any one dimension of less than 100 μm, with influents and effluents tending to have similar quantities of these smaller particles. As a single WWTP may release >100 billion MP particles annually, collectively WWTPs are significant contributors to the problem of MP pollution of global surface waters.

Well-developed ligand-binding assays demonstrate robust performance using singlet analysis.

Replicate sample testing has long been regarded as a necessity for bioanalytical laboratory testing, especially in the realm of ligand-binding assays (LBAs). In an era in which results were derived from crude test tube-based assays, the replication of results was warranted. Those assays were often imprecise and required multiple replicates to arrive at results that approached accuracy.

Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054.

Background: Pathological and genetic evidence implicates toxic effects of aggregated α-synuclein in the pathophysiology of neuronal dysfunction and degeneration in Parkinson's disease. Immunotherapy targeting aggregated α-synuclein is a promising strategy for delaying disease progression.

Objective: This study (NCT02459886) evaluated the safety, tolerability, and pharmacokinetics of BIIB054, a human-derived monoclonal antibody that preferentially binds to aggregated α-synuclein, in healthy volunteers and participants with Parkinson's disease.

Contribution to the risk characterization of ciguatoxins: LOAEL estimated from eight ciguatera fish poisoning events in Guadeloupe (French West Indies).

From 2010 to 2012, 35 ciguatera fish poisoning (CFP) events involving 87 individuals who consumed locally-caught fish were reported in Guadeloupe (French West Indies). For 12 of these events, the presence of ciguatoxins (CTXs) was indicated in meal remnants and in uncooked fish by the mouse bioassay (MBA). Caribbean ciguatoxins (C-CTXs) were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.

Assessment of the spatial distribution of soil microbial communities in patchy arid and semi-arid landscapes of the Negev Desert using combined PLFA and DGGE analyses.

Arid and semi-arid ecosystems are often characterized by vegetation patchiness and variable availability of resources. Phospholipid fatty acid (PLFA) and 16S rRNA gene fragment analyses were used to compare the bulk soil microbial community structure at patchy arid and semi-arid landscapes. Multivariate analyses of the PLFA data and the 16S rRNA gene fragments were in agreement with each other, suggesting that the differences between bulk soil microbial communities were primarily related to shrub vs intershrub patches, irrespective of climatic or site differences.

Three-dimensional culture of mouse renal carcinoma cells in agarose macrobeads selects for a subpopulation of cells with cancer stem cell or cancer progenitor properties.

The culture of tumor cell lines in three-dimensional scaffolds is considered to more closely replicate the in vivo tumor microenvironment than the standard method of two-dimensional cell culture. We hypothesized that our method of encapsulating and maintaining viable and functional pancreatic islets in agarose-agarose macrobeads (diameter 6-8 mm) might provide a novel method for the culture of tumor cell lines. In this report we describe and characterize tumor colonies that form within macrobeads seeded with mouse renal adenocarcinoma cells.

Hydrophilic agarose macrobead cultures select for outgrowth of carcinoma cell populations that can restrict tumor growth.

Cancer cells and their associated tumors have long been considered to exhibit unregulated proliferation or growth. However, a substantial body of evidence indicates that tumor growth is subject to both positive and negative regulatory controls. Here, we describe a novel property of tumor growth regulation that is neither species nor tumor-type specific.

Decompression syndrome (Caisson disease) in an Indian diver.

Acute decompression syndrome (Caisson's disease) is an acute neurological emergency in divers. It is caused due to release of nitrogen gas bubbles that impinge the blood vessels of the spinal cord and brain and result in severe neurodeficit. There are very few case reports in Indian literature.

Long-term results of external upper esophageal sphincter myotomy for oropharyngeal Dysphagia.

The aim of this work was to assess the efficacy of external myotomy of the upper esophageal sphincter (UES) for oropharyngeal dysphagia. In the period 1991-2006, 28 patients with longstanding dysphagia and/or aspiration problems of different etiologies underwent UES myotomy as a single surgical treatment. The main symptoms were difficulties in swallowing of a solid-food bolus, aspiration, and recurrent incidents of solid-food blockages.

Endoscopic carbon dioxide laser Zenker's diverticulotomy revisited.

Objectives: We assessed the efficacy of endoscopic Zenker's diverticulotomy with the carbon dioxide (CO2) laser and Acuspot and compared it with the historical results of using a CO2 laser without Acuspot and electrocautery diverticulotomy.

Methods: Between 1976 and 2005, a total of 229 endoscopic Zenker's diverticulotomies in 189 patients were performed in our institution. Since 1995, micro-endoscopic diverticulotomy with the CO2 laser and Acuspot (MEDCO2A) has been performed in 61 cases.