12-Hydroxyeicosatetraenoic acid is the only enzymatically produced HETE increased under brain ischemia.

Hydroxyeicosatetraenoic acids (HETE) are dramatically increased under brain ischemia and significantly affect post-ischemic recovery. However, the exact mechanism of HETE increase and their origin under ischemia are poorly understood. HETE might be produced de novo through lipoxygenase (LOX) -dependent synthesis with possible esterification into a lipid storage pool, or non-enzymatically through free radical oxidation of esterified arachidonic acid (20:4n6).

A simplified method for preventing postmortem alterations of brain prostanoids for true in situ level quantification.

Dramatic postmortem prostanoid (PG) enzymatic synthesis in the brain causes a significant artifact during PG analysis. Thus, enzyme deactivation is required for an accurate in situ endogenous PG quantification. To date, the only method for preventing postmortem brain PG increase with tissue structure preservation is fixation by head-focused microwave irradiation (MW), which is considered the gold standard method, allowing for rapid in situ heat-denaturation of enzymes.

Exogenous oxygen is required for prostanoid induction under brain ischemia as evidence for a novel regulatory mechanism.

Previously, we and others reported a rapid and dramatic increase in brain prostanoids (PG), including prostaglandins, prostacyclins, and thromboxanes, under ischemia that is traditionally explained through the activation of esterified arachidonic acid (20:4n6) release by phospholipases as a substrate for cyclooxygenases (COX). However, the availability of another required COX substrate, oxygen, has not been considered in this mechanism. To address this mechanism for PG upregulation through oxygen availability, we analyzed mouse brain PG, free 20:4n6, and oxygen levels at different time points after ischemic onset using head-focused microwave irradiation (MW) to inactivate enzymes in situ before craniotomy.

A shotgun metagenomic analysis of the fecal microbiome in humans infected with Giardia duodenalis.

Background: The mechanisms underlying the clinical outcome disparity during human infection with Giardia duodenalis are still unclear. In recent years, evidence has pointed to the roles of host factors as well as parasite's genetic heterogeneity as major contributing factors in the development of symptomatic human giardiasis. However, it remains contested as to how only a small fraction of individuals infected with G.

Strongyloides and COVID-19: Challenges and Opportunities for Future Research.

is a soil transmitted helminth endemic to tropical and subtropical areas that can persist for decades in immunocompetent human hosts as a chronic asymptomatic infection. The use of corticosteroids, a mainstay of treatment for patients hospitalized with severe coronavirus disease (COVID-19), can trigger a life-threatening Strongyloides hyperinfection syndrome and disseminated disease. We identified 22 previously published cases of strongyloidiasis occurring in individuals with COVID-19, with one death reported among the seven patients who had Strongyloides hyperinfection syndrome.

Connecting the Pipes: Agricultural Tile Drains and Elevated Imidacloprid Brain Concentrations in Juvenile Northern Leopard Frogs ().

Neonicotinoids are neurotoxic insecticides and are often released into nearby wetlands via subsurface tile drains and can negatively impact nontarget organisms, such as amphibians. Previous studies have indicated that imidacloprid, a commonly used neonicotinoid, can cross the amphibian blood-brain barrier under laboratory conditions; however, little is known about the impact of low concentrations in a field-based setting. Here, we report aqueous pesticide concentrations at wetland production areas that were either connected or not connected to agricultural tile drains, quantified imidacloprid and its break down products in juvenile amphibian brains and livers, and investigated the relationship between imidacloprid brain concentration and brain size.

Detection of imidacloprid and metabolites in Northern Leopard frog (Rana pipiens) brains.

Neonicotinoids are a new type of highly water-soluble insecticide used in agricultural practices to eliminate pests. Neonicotinoids bind almost irreversibly to postsynaptic nicotinic acetylcholine receptors in the central nervous system of invertebrates, resulting in overstimulation, paralysis, and death. Imidacloprid, the most commonly used neonicotinoid, is often transported to nearby wetlands through subsurface tile drains and has been identified as a neurotoxin in several aquatic non-target organisms.

Liver Bile Acid Changes in Mouse Models of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment. It is hypothesized to develop due to the dysfunction of two major proteins, amyloid-β (Aβ) and microtubule-associated protein, tau. Evidence supports the involvement of cholesterol changes in both the generation and deposition of Aβ.

Follow-Up of a Case of Dopamine-Mediated Yawning-Fatigue-Syndrome Responsive to Opioids, Successful Desensitization via Graded Activity Treatment.

A 60-year-old man suffering from recurrent attacks of yawning-fatigue-syndrome, triggered by mild exercise of his right leg since a temporary lumbar disc herniation 9 years ago, was initially treated with the oral µ-opioid-receptor agonist tilidine before each bout of exercise (see Dibaj et al. 2019 JAMA Neurology 2019;77:254). During the first few months, this treatment continuously prolonged the time without exercise-triggered yawning and fatigue.

Cyclooxygenase inhibition attenuates brain angiogenesis and independently decreases mouse survival under hypoxia.

Although cyclooxygenase (COX) role in cancer angiogenesis has been studied, little is known about its role in brain angioplasticity. In the present study, we chronically infused mice with ketorolac, a non-specific COX inhibitor that does not cross the blood-brain barrier (BBB), under normoxia or 50% isobaric hypoxia (10% O by volume). Ketorolac increased mortality rate under hypoxia in a dose-dependent manner.

[Management of patients with chronic pain in acute and perioperative medicine : An interdisciplinary challenge].

Chronic pain is a frequent comorbidity of patients in hospitals and has an influence on the clinical course and the duration of hospitalization. There is a need to have a better understanding of chronic pain as a comorbidity and it should be considered to a greater extent in understanding diseases, in treatment concepts and hospital structures to ensure a resource-oriented and high-quality care. This begins on admission by identifying pre-existing pain and related risk factors with the medical history and taking these into account in the treatment regimen.

Blood-Brain Barrier Is the Major Site for a Rapid and Dramatic Prostanoid Increase upon Brain Global Ischemia.

We and others have demonstrated a rapid and dramatic increase in brain prostanoids upon decapitation-induced brain global ischemia and injury. However, the mechanism for this induction, including the cell types involved, are unknown. In the present study, we have validated and applied a pharmacological approach to inhibit prostanoid synthesis in the blood-brain barrier including endothelial cells.

Sterol Carrier Protein-2/Sterol Carrier Protein-x/Fatty Acid Binding Protein-1 Ablation Impacts Response of Brain Endocannabinoid to High-Fat Diet.

Brain endocannabinoids (EC) such as arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) primarily originate from serum arachidonic acid (ARA), whose level is regulated in part by a cytosolic ARA-binding protein, that is, liver fatty acid binding protein-1 (FABP1), not expressed in the brain. Ablation of the Fabp1 gene (LKO) increases brain AEA and 2-AG by decreasing hepatic uptake of ARA to increase serum ARA, thereby increasing ARA availability for uptake by the brain. The brain also expresses sterol carrier protein-2 (SCP-2), which is also a cytosolic ARA-binding protein.

Expressions as signs and their significance for emotional development.

For research on emotional development, defining emotions as psychological systems of appraisals, expressions, body reactions, and subjective feelings in all phases of ontogenesis raises tricky methodological issues. How can we measure single emotions when appraisals and feelings cannot be assessed from outside, when expressions do not seem to be tied unequivocally to single emotions, and feelings are sometimes decoupled from perceivable expressions? Furthermore, how does a restricted set of neonate emotions differentiate into a culturally modified set of adult emotions? This article presents an innovative answer to these issues by applying Vygotsky's culture-historical approach on the psychological significance of social signs to the analysis of emotion, expression, and their development. The core assumption is that humans learn to use emotional expressions as communicative signs that appeal to another person to regulate their interaction through emotions and as psychological signs that appeal to the self to regulate the self's actions through emotions.

Psychometric Properties of Pressure Pain Thresholds Measured in 2 Positions for Adults With and Without Neck-Shoulder Pain and Tenderness.

Objective: The purpose of this study was to determine the psychometric properties of pressure pain threshold (PPT) testing in adults with and without neck-shoulder pain and tenderness and to compare the differences in PPT measurements between the seated and prone positions.

Methods: Thirty asymptomatic adults and 30 symptomatic patients with intermittent neck-shoulder pain and tenderness completed the study. A pressure algometer was used to assess PPTs at specific points on the middle deltoid, levator scapulae, and upper trapezius muscles of the dominant side of the asymptomatic individuals and the painful side of the patients.

[Cross-sectoral interdisciplinary multimodal pain therapy : Recommendations on structural and process parameters of the ad hoc commission "Interdisciplinary Multimodal Pain Therapy" of the German Pain Society (Deutsche Schmerzgesellschaft e. V.)].

Based on the fundamental concept of the biopsychosocial model, interdisciplinary multimodal pain therapy (IMPT) has developed to one of the most important components in the treatment of patients suffering from chronic pain. The process criteria for IMPT in Germany are described in the German OPS catalogue and IMPT is mainly offered as an inpatient treatment only. This article updates some of the fundamental criteria for IMPT for adult inpatient treatment and the task force defines basic structural and process criteria for the implementation of IMPT for outpatients.

Scp-2/Scp-x ablation in Fabp1 null mice differentially impacts hepatic endocannabinoid level depending on dietary fat.

Dysregulation of the hepatic endocannabinoid (EC) system and high fat diet (HFD) are associated with non-alcoholic fatty liver disease. Liver cytosol contains high levels of two novel endocannabinoid binding proteins-liver fatty acid binding protein (FABP1) and sterol carrier protein-2 (SCP-2). While Fabp1 gene ablation significantly increases hepatic levels of arachidonic acid (ARA)-containing EC and sex-dependent response to pair-fed high fat diet (HFD), the presence of SCP-2 complicates interpretation.

Comparative effects of high oleic acid vs high mixed saturated fatty acid obesogenic diets upon PUFA metabolism in mice.

Emerging evidence indicates that the fatty acid composition of obesogenic diets influences physiologic outcomes. There are scant data regarding how the content of non-essential fatty acids like monounsaturated fatty acids (MUFA) and saturated fatty acids (SFAs) impact the metabolism of polyunsaturated fatty acids (PUFAs). In this work, we tested the hypothesis that obesogenic diets enriched in oleic acid (OA; 18:1n-9) reduce polyunsaturated fatty acid (PUFA) levels vs an obesogenic diet enriched in SFAs.

Graded Activity for Older Adults with Chronic Low Back Pain: Program Development and Mixed Methods Feasibility Cohort Study.

Background: Persistent pain is highly prevalent in older adults and can lead to functional limitations in activities of daily living, and to psychosocial distress. There is a lack of established active therapy programs, especially for older adults with chronic pain.

Objectives: To develop a graded activity program and to evaluate its feasibility within a pilot study.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids.

Astrocyte arachidonate and palmitate uptake and metabolism is differentially modulated by dibutyryl-cAMP treatment.

Astrocytes play a vital role in brain lipid metabolism; however the impact of the phenotypic shift in astrocytes to a reactive state on arachidonic acid metabolism is unknown. Therefore, we determined the impact of dibutyryl-cAMP (dBcAMP) treatment on radiolabeled arachidonic acid ([1-(14)C]20:4n-6) and palmitic acid ([1-(14)C]16:0) uptake and metabolism in primary cultured murine cortical astrocytes. In dBcAMP treated astrocytes, total [1-(14)C]20:4n-6 uptake was increased 1.

Mitochondrial Glycerol-3-Phosphate Acyltransferase-Dependent Phospholipid Synthesis Modulates Phospholipid Mass and IL-2 Production in Jurkat T Cells.

Changes in glycerophospholipid metabolism with age and disease can have a profound effect on immune cell activation and effector function. We previously demonstrated that glycerol-3-phosphate acyltransferase-1, the first and rate limiting step in de novo glycerophospholipid synthesis, plays a role in modulating murine T cell function. The resultant phenotype is characterized by decreased IL-2 production, increased propensity toward apoptosis, and altered membrane glycerophospholipid mass similar to that of an aged T cell.

Mouse Strain Impacts Fatty Acid Uptake and Trafficking in Liver, Heart, and Brain: A Comparison of C57BL/6 and Swiss Webster Mice.

C57BL/6 and Swiss Webster mice are used to study lipid metabolism, although differences in fatty acid uptake between these strains have not been reported. Using a steady state kinetic model, [1-(14)C]16:0, [1-(14)C]20:4n-6, or [1-(14)C]22:6n-3 was infused into awake, adult male mice and uptake into liver, heart, and brain determined. The integrated area of [1-(14)C]20:4n-6 in plasma was significantly increased in C57BL/6 mice, but [1-(14)C]16:0 and [1-(14)C]22:6n-3 were not different between groups.