The lipid-laden macrophage index (LLMI) is a semiquantitative test used to evaluate aspiration in children. We assessed the reliability and reproducibility of LLMI by calculating interobserver and intraobserver variability among pathologists, with and without expertise in cytopathology. Forty-nine bronchoalveolar washes/lavages were blindly reviewed by four reviewers and assigned an LLMI. Three pathologists (two cytopathologists, one pathology fellow) reviewed slides twice and one cytotechnologist reviewed them once. Intraclass correlation coefficient (ICC) with 95% confidence interval (C.I.) was used to measure overall intraobserver and interobserver agreement. Interobserver agreement was also calculated separately for each pair of reviewers. ICC values did not indicate an acceptable level of interobserver agreement among pathologists, with (ICC = 0.67, 95% C.I.: 0.56-0.77) and without (ICC = 0.77, 95% C.I.: 0.61-0.84) the cytotechnologist included in the analysis. An ICC of 0.84 (95% C.I.: 0.78-0.89) indicated an acceptable level of intraobserver agreement among pathologists. When calculated separately for each pair of reviewers, all but two ICC values for interobserver agreement were less than 0.75 (the minimally acceptable value for a reliable clinical measurement), and the lower confidence limit of each of the 95% C.I. was far below the 0.75 cutoff. Using Lin's coefficient, intraobserver variability was only acceptable for two pathologists. Our study highlights the lack of precision and subjectivity of the LLMI, as well as the significant inter and intraobserver bias that may occur among experienced and inexperienced pathologists, and cytotechnologists. Clinicians and cytopathologists alike should be mindful of this potential pitfall and interpret LLMI scores with caution.
Chemical signaling is ubiquitous and employs a variety of receptor types to detect the cacophony of molecules relevant for each living organism. Insects, our most diverse taxon, have evolved unique olfactory receptors with as little as 10% sequence identity between receptor types. We have identified a promiscuous volatile, 2-methyltetrahydro-3-furanone (coffee furanone), that elicits chemosensory and behavioral activity across multiple insect orders and receptors.
In vivo
and
in vitro
physiology showed that coffee furanone was detected by roughly 80% of the recorded neurons expressing the insect-specific olfactory receptor complex in the antenna of
Drosophila melanogaster
, at concentrations similar to other known, and less promiscuous, ligands. Neurons expressing specialized receptors, other chemoreceptor types, or mutants lacking the complex entirely did not respond to this compound. This indicates that coffee furanone is a promiscuous ligand for the insect olfactory receptor complex itself and did not induce non-specific cellular responses. In addition, we present homology modeling and docking studies with selected olfactory receptors that suggest conserved interaction regions for both coffee furanone and known ligands. Apart from its physiological activity, this known food additive elicits a behavioral response for several insects, including mosquitoes, flies, and cockroaches. A broad-scale behaviorally active molecule non-toxic to humans thus has significant implications for health and agriculture. Coffee furanone serves as a unique tool to unlock molecular, physiological, and behavioral relationships across this diverse receptor family and animal taxa.
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