EphrinB-EphB receptor tyrosine kinases have been demonstrated to play important roles in pain processing after peripheral nerve injury. We have previously reported that ephrinB-EphB receptor signaling can regulate excitability and plasticity of neurons in spinal dorsal horn, and thus contribute to spinal central sensitization in neuropathic pain. How EphB receptor activation influences excitability of primary neurons in dorsal root ganglion (DRG), however, remains unknown. Here we report that EphB receptor activation facilitates calcium influx through NMDA receptor dependent and independent manners. In cultured DRG cells from adult rats, EphB1 and EphB2 receptors were expressed in neurons, but not the glial cells. Bath application of EphB receptor agonist ephrinB2-Fc induced NMDA-independent Ca influx, which was from the extracellular space rather than endoplasmic reticulum. EphB receptor activation also greatly enhanced NMDA-dependent Ca influx and NR2B phosphorylation, which was prevented by pre-treatment of Src kinase inhibitor PP2. In nerve-injured DRG neurons, elevated expression and activation of EphB1 and EphB2 receptors contributed to the increased intracellular Ca concentration and NMDA-induced Ca influx. Repetitive intrathecal administration of EphB2-Fc inhibited the increased phosphorylation of NR2B and Ca-dependent subsequent signals Src, ERK, and CaMKII as well as behaviorally expressed pain after nerve injury. These findings demonstrate that activation of EphB receptors can modulate DRG neuron excitability by facilitating Ca influx directly or through Src kinase activation-mediated NMDA receptor phosphorylation and that EphB receptor activation is critical to DRG neuron hyperexcitability, which has been considered critical to the subsequent spinal central sensitization and neuropathic pain.Upon transient musculoskeletal diseases, some patients develop persistent pain while others recover from pain. Here we studied whether such heterogeneity also occurs in rats after recovery from unilateral antigen-induced arthritis (AIA) in the knee joint, and which pain phenotype may predict the course of pain. Typically inflammatory swelling lasts about three weeks. Pain-related behaviors were monitored for 84 days after AIA induction. Unbiased cluster analysis of intra-group-differences at day 84 of AIA revealed that about one third of the rats (cluster 1) showed persistent mechanical hyperalgesia at the injected knee joint, whereas the other rats (cluster 2) had recovered from pain. Retrograde analysis of pain-related behaviors revealed that cluster 1 rats exhibited more severe mechanical hyperalgesia at the injected knee from day 3 of AIA, and mechanical hyperalgesia at the contralateral knee. Cluster 1 and 2 rats did not show different inflammatory swelling, secondary mechanical and thermal hyperalgesia at the ipsilateral hindpaw, guarding score and asymmetry of weight bearing during AIA. Thus in particular early severe mechanical hyperalgesia in the inflamed joint and segmental contralateral mechanical hyperalgesia seem to be a risk factor for the development of persistent mechanical hyperalgesia pointing to the importance of spinal mechanisms. However, none of the rats showed an expression of ATF3 in DRG neurons, nor morphological spinal microglia activation thus not suggesting development of neuropathic pain. Both clusters showed a persistent upregulation of pCREB in DRG neurons, inversely correlated with mechanical hyperalgesia at the knee. The role of pCREB needs to be further explored.BACKGROUND Diabetic foot ulcers with associated infection and osteomyelitis often lead to partial or complete limb loss. Determination of the appropriate level for amputation based on the patient's baseline physical function, extent of infection, vascular patency, and comorbidities can be challenging. Although Chopart amputation preserves greater limb length than more proximal alternatives such as Syme or below-the-knee amputations (BKA), challenges with wound healing and prosthesis fitting have been reported. We aimed to investigate the functional and clinical outcomes of Chopart amputation combined with tendon transfers. METHODS We identified patients who underwent Chopart amputations for diabetic foot infections by an academic orthopaedic group between August 2013 and September 2018. Subjects completed three Patient-Reported Outcomes Measurement Information Systems (PROMIS) instruments. Incidence of postoperative complications and change in patient-reported outcomes before and after surgery were recorded. fter wound healing, Chopart amputees may struggle with obtaining a prosthesis suitable for ambulation. Surgeons should exercise judicious patient selection before performing Chopart amputation. LEVEL OF EVIDENCE IV, Case Series.OBJECTIVES Reducing avoidable radiation exposure during medical procedures is a top priority. The purpose of this study was to quantify, for the first time, the percentage of avoidable radiation during fluoroscopically guided cardiovascular interventions using eye tracking technologies. MATERIALS AND METHODS Mobile eye tracking glasses were used to measure precisely when the operators looked at a fluoroscopy screen during the interventions.  https://www.selleckchem.com/products/abt-199.html  A novel machine learning algorithm and image processing techniques were used to automatically analyze the data and compute the percentage of avoidable radiation. Based on this percentage, the amount of potentially avoidable radiation dose was computed. RESULTS This study included 30 cardiovascular interventions performed by 5 different operators. A significant percentage of the administered radiation (mean [SD], 43.5% [12.6%]) was avoidable (t29 = 18.86, P less then 0.00001); that is, the operators were not looking at the fluoroscopy screen while the x-ray was on. On average, this corresponded to avoidable amounts of air kerma (mean [SD], 229 [66] mGy) and dose area product (mean [SD], 32,781 [9420] mGycm), or more than 11 minutes of avoidable x-ray usage, per procedure. CONCLUSIONS A significant amount of the administered radiation during cardiovascular interventions is in fact avoidable.