Significance Adult hippocampal neurogenesis underpins learning, memory, and mood but diminishes with age and certain illnesses. The orphan nuclear receptor TLX/NR2E1 regulates neural stem and progenitor cell self-renewal and proliferation, but its orphan status has hindered its utilization as a therapeutic target to modulate adult neurogenesis. Here, we deorphanize TLX and report that oleic acid is an endogenous, metabolic ligand of TLX. These findings open avenues for future therapeutic modulation of TLX to counteract cognitive and mental decline in aging and diseases associated with decreased neurogenesis.
Background Smell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID-19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID-19 patients suggests that self-reported measures are insufficient for capturing patients with chemosensory dysfunction. Objectives The purpose of this study was to quantify the impact of recent COVID-19 infection on chemosensory function and demonstrate the use of at-home objective smell and taste testing in an at-risk population of healthcare workers. Methods Two hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self-administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one-month follow-up surveys were completed. Results Among subjects with prior SARS-CoV-2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self-reported smell and taste loss were both strong predictors of COVID-19 positivity. Subjects with evidence of recent SARS-CoV-2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time-dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab. Conclusion Healthcare workers with recent SARS-CoV-2 infection had reduced olfaction and normal gustation on self-administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.
Polycyclic aromatic hydrocarbons (PAHs) have long been recognized as important environmental toxicants. Despite a plethora of information on the fate and effects of parent PAHs, relatively little is known about the environmental fate and toxicity of ketone- and quinone-substituted PAH oxidation products (termed oxy-PAHs), particularly in the aquatic environment. This study begins to fill that gap using embryos of the Japanese medaka (Oryzias latipes) as a model species. The genotoxic potential of two environmentally relevant oxy-PAHs, acenaphthenequinone and 7,12-benz[a]anthracenquinone, was assessed using the comet assay. We found that both oxy-PAHs could cause significant increases in DNA damage after only 48 h of exposure at the lowest concentrations tested (5 μg/L). Comparisons of the genotoxic potential between these oxy-PAHs and their corresponding parent PAHs (acenaphthene and benz[a]anthracene) and a well-known mutagenic PAH, benzo[a]pyrene, indicated similar potencies among all five of these compounds, particularly after longer (7 day) exposures. This study demonstrates the mutagenic potential of oxy-PAHs to an in vivo fish embryo model and points out the need for further study of their environmental occurrence and biologic effects.
Objectives/Hypothesis Intubation with inappropriately sized endotracheal tubes (ETT) can cause long‐term tracheal and laryngeal injuries often requiring surgical intervention. Although tracheal size has been demonstrated to vary based on height and sex, it is unclear whether these guidelines are regularly implemented in patients undergoing endotracheal intubation. The objective of this study is to determine the rate of appropriate ETT size selection in patients undergoing intubation and assess provider decision making in ETT size selection. Study Design Retrospective cohort study. Methods The study population was all patients who underwent endotracheal intubation over a two‐week period at a tertiary academic medical center. Data were collected on patient age, gender, height, BMI, comorbidities, ETT size, duration of intubation, bronchoscopies, and type of practitioner who performed the intubation. A height‐based nomogram for ETT size selection was used to determine the recommended ETT size for each patient. Results One hundred five patients met the inclusion criteria. 22% of patients were intubated with an inappropriately large tube, defined as 1.0 mm larger than the recommended size. Women were more likely to be intubated with an inappropriately large ETT (OR = 13.58, P = .001), as were patients with height less than 160 cm (OR = 141, P = .001). Other factors related to disease severity, anticipation for bronchoscopy, and BMI were not risk factors for the use of inappropriately large ETT. Conclusions Although there is compelling evidence that height is a strong predictor of tracheal morphology and appropriate ETT size, height‐based guidelines have yet to be universally adopted for ETT size selection. Laryngoscope, 131:1967–1971, 2021
Adult hippocampal neurogenesis underpins learning, memory, and mood, but diminishes with age and illness. The orphan nuclear receptor TLX/NR2E1 is known to regulate neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is unknown. We found that neural stem and progenitor cells require monounsaturated fatty acids to survive and proliferate. Specifically, oleic acid (18:1ω9) binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell cycle and neurogenesis genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation. These findings pave the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.
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