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ABSTRACT
Sleep deprivation promotes tumor growth through loss of daily rhythms in cellular lipid metabolism.
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Neoplasms , Sleep Deprivation , Sleep , Humans , Neoplasms/metabolism , Sleep/physiology , Animals , Sleep Deprivation/metabolism , Sleep Deprivation/physiopathology , Lipid Metabolism , Circadian Rhythm/physiologyABSTRACT
Humans use cannabinoid drugs to alleviate pain. As cannabis and cannabinoids are legalized in the United States for medicinal and recreational use, it has become critical to determine the potential utilities and harms of cannabinoid drugs in individuals living with chronic pain. Here, we tested the effects of repeated ∆9-tetrahydrocannabinol (THC) vapor inhalation on thermal nociception and mechanical sensitivity, in adult male and female Wistar rats using a chronic inflammatory pain model (ie, treated with complete Freund's adjuvant [CFA]). We report that repeated THC vapor inhalation rescues thermal hyperalgesia in males and females treated with CFA and also reduces mechanical hypersensitivity in CFA males but not females. Many of the antihyperalgesic effects of chronic THC vapor were still observable 24 hours after cessation of the last THC exposure. We also report plasma levels of THC and its major metabolites, some of which are cannabinoid type-1 receptor agonists, after the first and tenth days of THC vapor inhalation. Finally, we report that systemic administration of the cannabinoid type-1 receptor inverse agonist AM251 (1 mg/kg, I.P.) blocks the antihyperalgesic effects of THC vapor in males and females. These data provide a foundation for future work that will explore the cells and circuits underlying the antihyperalgesic effects of THC vapor inhalation in individuals with chronic inflammatory pain. PERSPECTIVE: Cannabinoids are thought to have potential utility in the treatment of chronic pain, but few animal studies have tested the effects of chronic THC or cannabis in animal models of chronic pain. We tested the effects of repeated THC vapor inhalation on chronic pain-related outcomes in male and female animals.
ABSTRACT
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ABSTRACT
Nitrate, a prevalent water pollutant, poses substantial public health concerns and environmental risks. Electrochemical reduction of nitrate (eNO3RR) has emerged as an effective alternative to conventional biological treatments. While extensive lab work has focused on designing efficient electrocatalysts, implementation of eNO3RR in practical wastewater settings requires careful consideration of the effects of various constituents in real wastewater. In this critical review, we examine the interference of ionic species commonly encountered in electrocatalytic systems and universally present in wastewater, such as halogen ions, alkali metal cations, and other divalent/trivalent ions (Ca2+, Mg2+, HCO3-/CO32-, SO42-, and PO43-). Notably, we categorize and discuss the interfering mechanisms into four groups: (1) loss of active catalytic sites caused by competitive adsorption and precipitation, (2) electrostatic interactions in the electric double layer (EDL), including ion pairs and the shielding effect, (3) effects on the selectivity of N intermediates and final products (N2 or NH3), and (4) complications by the hydrogen evolution reaction (HER) and localized pH on the cathode surface. Finally, we summarize the competition among different mechanisms and propose future directions for a deeper mechanistic understanding of ionic impacts on eNO3RR.
Subject(s)
Nitrates , Nitrates/chemistry , Catalysis , Ions , Wastewater/chemistry , Oxidation-Reduction , Water Pollutants, Chemical/chemistryABSTRACT
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Contact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis upon metabolic demands. Detection of these contact sites at the nanometer scale over time in living cells is challenging. We developed a tool kit for detecting contact sites based on fluorogen-activated bimolecular complementation at CONtact sites, FABCON, using a reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic regulation.
Subject(s)
Endoplasmic Reticulum , Lipid Droplets , Mitochondria , Lipid Droplets/metabolism , Humans , Endoplasmic Reticulum/metabolism , Mitochondria/metabolism , Mitochondria/genetics , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Lipid Metabolism , HeLa Cells , HEK293 Cells , Luminescent Proteins/metabolism , Luminescent Proteins/geneticsABSTRACT
Opioids trigger myelin insulation of reward circuit axons in a feedforward loop of addiction.
Subject(s)
Analgesics, Opioid , Humans , Analgesics, Opioid/pharmacology , Animals , Axons/metabolism , Axons/physiology , Myelin Sheath/metabolism , Reward , Opioid-Related DisordersABSTRACT
STUDY OBJECTIVE: To investigate the association between race and route of hysterectomy among patients undergoing hysterectomy for abnormal uterine bleeding (AUB) in the absence of uterine myoma disease and excluding malignancy. DESIGN: A cross-sectional cohort study utilizing the Healthcare Cost and Utilization Project Nationwide Inpatient Sample and National Ambulatory Surgical databases to compare abdominal to minimally invasive routes of hysterectomy. SETTING: Hospitals and hospital-affiliated ambulatory surgical centers participating in the Healthcare Cost and Utilization Project in 2019. PATIENTS: A total of 75 838 patients who had undergone hysterectomy for AUB, excluding uterine myoma and malignancy. INTERVENTIONS: n/a MEASUREMENTS AND MAIN RESULTS: Of the 75 838 hysterectomies performed for AUB in the absence of uterine myomas and malignancy, 10.1% were performed abdominally and 89.9% minimally invasively. After adjusting for confounders, Black patients were 38% more likely to undergo abdominal hysterectomy compared to White patients (OR 1.38, CI 1.12-1.70 p = .002). Black race, thus, is independently associated with open surgery. CONCLUSION: Despite excluding uterine myomas as a risk factor for an abdominal route of hysterectomy, Black race remained an independent predictor for abdominal versus minimally invasive hysterectomy, and Black patients were found to undergo a disproportionately higher rate of abdominal hysterectomy compared to White patients.
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Background Imposter phenomenon (IP) is common in medicine. An intervention from the business world, the Reflected Best Self Exercise (RBSE), in which an individual elicits stories of themselves at their best, has not been studied in medical residents. Objective To determine the feasibility of implementing the RBSE and its potential for reducing IP in residents. Methods All incoming internal medicine and medicine-pediatrics interns in the 2022-2023 academic year at a single institution were invited to complete the RBSE. Participants elicited stories from contacts prior to beginning residency and received their stories during intern orientation in a 1-hour session led by one author with no prior training. Cost and time requirements were assessed. IP was measured via the Clance Impostor Phenomenon Scale (CIPS) at baseline, 1 month, and 6 months following the RBSE. Informal feedback on the RBSE was collected via surveys at 1 month and 6 months. Results Nineteen of 35 interns (54.3%) completed the RBSE. It cost $75 per participant, for a total cost of $1,425. Twenty-eight of 35 (80%) completed the baseline CIPS, with scores similar between participants and nonparticipants (64.9 vs 68.9). CIPS scores were lower in participants at 1 month (57.6 vs 69.6) and 6 months (55.6 vs 64.5) but did not meet statistical significance. Survey feedback from participants suggested the intervention was beneficial. Conclusions Implementing the RBSE in residents was feasible with reasonable cost and time commitment. It appeared highly acceptable to residents, with some promise of effects on an IP scale.
Subject(s)
Internal Medicine , Internship and Residency , Humans , Internal Medicine/education , Surveys and Questionnaires , Female , Male , Self Concept , Pediatrics/education , Adult , Feasibility Studies , Education, Medical, Graduate , Anxiety DisordersABSTRACT
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ABSTRACT
Astrocyte-secreted neurocan guides the formation of inhibitory circuits in the brain.
Subject(s)
Synapses , Synapses/physiology , Synapses/metabolism , Humans , Animals , Neuroglia/metabolism , Neuroglia/physiology , Neuroglia/cytology , Astrocytes/metabolism , Astrocytes/cytology , Astrocytes/physiology , Neurogenesis/physiology , Brain/physiology , Brain/metabolismABSTRACT
Highlights from the Science family of journals.
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Highlights from the Science family of journals.
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Glia take up and detoxify neurotoxic lipids on a wake-sleep cycle, in turn promoting healthy sleep.
Subject(s)
Neuroglia , Sleep , Animals , Humans , Neuroglia/metabolism , Neuroglia/physiology , Sleep/physiology , Wakefulness/physiologyABSTRACT
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The Mars Sample Return mission intends to retrieve a sealed collection of rocks, regolith, and atmosphere sampled from Jezero Crater, Mars, by the NASA Perseverance rover mission. For all life-related research, it is necessary to evaluate water availability in the samples and on Mars. Within the first Martian year, Perseverance has acquired an estimated total mass of 355 g of rocks and regolith, and 38 µmoles of Martian atmospheric gas. Using in-situ observations acquired by the Perseverance rover, we show that the present-day environmental conditions at Jezero allow for the hydration of sulfates, chlorides, and perchlorates and the occasional formation of frost as well as a diurnal atmospheric-surface water exchange of 0.5-10 g water per m2 (assuming a well-mixed atmosphere). At night, when the temperature drops below 190 K, the surface water activity can exceed 0.5, the lowest limit for cell reproduction. During the day, when the temperature is above the cell replication limit of 245 K, water activity is less than 0.02. The environmental conditions at the surface of Jezero Crater, where these samples were acquired, are incompatible with the cell replication limits currently known on Earth.
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Blocking complement signaling biases microglia to destroy amyloid aggregates, not neuronal synapses.
Subject(s)
Alzheimer Disease , Microglia , Humans , Neurons , Signal Transduction , SynapsesABSTRACT
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