The utility of vertebral Hounsfield units as a prognostic indicator of adverse events following treatment of spinal epidural abscess.

Background: Spinal epidural abscesses (SEAs) are a devastating condition with high levels of associated morbidity and mortality. Hounsfield units (HUs), a marker of radiodensity on CT scans, have previously been correlated with adverse events following spinal interventions. We evaluated whether HUs might also be associated with all-cause complications and/or mortality in this high-risk population. Methods: This retrospective cohort study was carried out within an academic health system in the United States. Adults diagnosed with a SEA between 2006 and 2021 and who also had a CT scan characterizing their SEA within 6 months of diagnosis were considered. HUs were abstracted from the 4 vertebral bodies nearest to, but not including, the infected levels. Our primary outcome was the presence of composite 90-day complications and HUs represented the primary predictor. A multivariable logistic regression analysis was conducted adjusting for demographic and disease-specific confounders. In sensitivity testing, separate logistic regression analyses were conducted (1) in patients aged 65 and older and (2) with mortality as the primary outcome. Results: Our cohort consisted of 399 patients. The overall incidence of 90-day complications was 61.2% (n=244), with a 7.8% (n=31) 90-day mortality rate. Those experiencing complications were more likely to have undergone surgery to treat their SEA (58.6% vs. 46.5%; p=.018) but otherwise the cohorts were similar. HUs were not associated with composite 90-day complications (Odds ratio [OR] 1.00 [95% CI 1.00-1.00]; p=.842). Similar findings were noted in sensitivity testing. Conclusions: While HUs have previously been correlated with adverse events in certain clinical contexts, we found no evidence to suggest that HUs are associated with all-cause complications or mortality in patients with SEAs. Future research hoping to leverage 3-dimensional imaging as a prognostic measure in this patient population should focus on alternative targets. Level of Evidence: Level III; Observational Cohort study.

Input density tunes Kenyon cell sensory responses in the Drosophila mushroom body.

The ability to discriminate sensory stimuli with overlapping features is thought to arise in brain structures called expansion layers, where neurons carrying information about sensory features make combinatorial connections onto a much larger set of cells. For 50 years, expansion coding has been a prime topic of theoretical neuroscience, which seeks to explain how quantitative parameters of the expansion circuit influence sensory sensitivity, discrimination, and generalization. Here, we investigate the developmental events that produce the quantitative parameters of the arthropod expansion layer, called the mushroom body. Using Drosophila melanogaster as a model, we employ genetic and chemical tools to engineer changes to circuit development. These allow us to produce living animals with hypothesis-driven variations on natural expansion layer wiring parameters. We then test the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input density, but not cell number, tunes neuronal odor selectivity. Simple odor discrimination behavior is maintained when the Kenyon cell number is reduced and augmented by Kenyon cell number expansion. Animals with increased input density to each Kenyon cell show increased overlap in Kenyon cell odor responses and become worse at odor discrimination tasks.

Hacking brain development to test models of sensory coding.

Animals can discriminate myriad sensory stimuli but can also generalize from learned experience. You can probably distinguish the favorite teas of your colleagues while still recognizing that all tea pales in comparison to coffee. Tradeoffs between detection, discrimination, and generalization are inherent at every layer of sensory processing. During development, specific quantitative parameters are wired into perceptual circuits and set the playing field on which plasticity mechanisms play out. A primary goal of systems neuroscience is to understand how material properties of a circuit define the logical operations-computations--that it makes, and what good these computations are for survival. A cardinal method in biology-and the mechanism of evolution--is to change a unit or variable within a system and ask how this affects organismal function. Here, we make use of our knowledge of developmental wiring mechanisms to modify hard-wired circuit parameters in the Drosophila melanogaster mushroom body and assess the functional and behavioral consequences. By altering the number of expansion layer neurons (Kenyon cells) and their dendritic complexity, we find that input number, but not cell number, tunes odor selectivity. Simple odor discrimination performance is maintained when Kenyon cell number is reduced and augmented by Kenyon cell expansion.

May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression.

How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.