Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture,DNA sequencing and microscopy

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra‐operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six‐month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be ‘clean/non‐infected’ were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA‐FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal ‘clean’ margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post‐operative approaches, correlating any outcomes back to culture‐sequence findings.     

An uncertainty principle for neural coding: Conjugate representations of position and velocity are mapped onto firing rates and co‐firing rates of neural spike trains

The hippocampal system contains neural populations that encode an animal's position and velocity as it navigates through space. Here, we show that such populations can embed two codes within their spike trains: a firing rate code ( R ) conveyed by within‐cell spike intervals, and a co‐firing rate code () conveyed by between‐cell spike intervals. These two codes behave as conjugates of one another, obeying an analog of the uncertainty principle from physics: information conveyed in R comes at the expense of information in , and vice versa. An exception to this trade‐off occurs when spike trains encode a pair of conjugate variables, such as position and velocity, which do not compete for capacity across R and . To illustrate this, we describe two biologically inspired methods for decoding R and , referred to as sigma and sigma‐chi decoding, respectively. Simulations of head direction and grid cells show that if firing rates are tuned for position (but not velocity), then position is recovered by sigma decoding, whereas velocity is recovered by sigma‐chi decoding. Conversely, simulations of oscillatory interference among theta‐modulated “speed cells” show that if co‐firing rates are tuned for position (but not velocity), then position is recovered by sigma‐chi decoding, whereas velocity is recovered by sigma decoding. Between these two extremes, information about both variables can be distributed across both channels, and partially recovered by both decoders. These results suggest that populations with different spatial and temporal tuning properties—such as speed versus grid cells—might not encode different information, but rather, distribute similar information about position and velocity in different ways across R and . Such conjugate coding of position and velocity may influence how hippocampal populations are interconnected to form functional circuits, and how biological neurons integrate their inputs to decode information from firing rates and spike correlations.     

Perisynaptic Schwann cells phagocytose nerve terminal debris in a mouse model of Guillain‐Barré syndrome

In mouse models of acute motor axonal neuropathy, anti‐ganglioside antibodies (AGAbs) bind to motor axons, notably the distal nerve, and activate the complement cascade. While complement activation is well studied in this model, the role of inflammatory cells is unknown. Herein we aimed to investigate the contribution of phagocytic cells including macrophages, neutrophils and perisynaptic Schwann cells (pSCs) to distal nerve pathology. To observe this, we first created a subacute injury model of sufficient duration to allow inflammatory cell recruitment. Mice were injected intraperitoneally with an anti‐GD1b monoclonal antibody that binds strongly to mouse motor nerve axons. Subsequently, mice received normal human serum as a source of complement. Dosing was titrated to allow humane survival of mice over a period of 3 days, yet still induce the characteristic neurological impairment. Behaviour and pathology were assessed in vivo using whole‐body plethysmography and post‐sacrifice by immunofluorescence and flow cytometry. ex vivo nerve‐muscle preparations were used to investigate the acute phagocytic role of pSCs following distal nerve injury. Following complement activation at distal intramuscular nerve sites in the diaphragm macrophage localisation or numbers are not altered, nor do they shift to a pro‐ or anti‐inflammatory phenotype. Similarly, neutrophils are not significantly recruited. Instead, ex vivo nerve‐muscle preparations exposed to AGAb plus complement reveal that pSCs rapidly become phagocytic and engulf axonal debris. These data suggest that pSCs, rather than inflammatory cells, are the major cellular vehicle for axonal debris clearance following distal nerve injury, in contrast to larger nerve bundles where macrophage‐mediated clearance predominates.