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In adult primary visual cortex (V1), dendritic spines are more persistent than during development. Brain-derived neurotrophic factor (BDNF) increases synaptic strength, and its levels rise during cortical development. We therefore asked whether postsynaptic BDNF signaling through its receptor TrkB regulates spine persistence in adult V1. This question has been difficult to address because most methods used to alter TrkB signaling in vivo affect cortical development or cannot distinguish between pre-and postsynaptic mechanisms. We circumvented these problems by employing transgenic mice expressing a dominant negative TrkB-EGFP fusion protein in sparse pyramidal neurons of the adult neocortex and hippocampus, producing a Golgi-staining-like pattern. In adult V1, expression of dominant negative TrkB-EGFP resulted in reduced mushroom spine maintenance and synaptic efficacy, accompanied by an increase in long and thin spines and filopodia. In contrast, mushroom spine maintenance was unaffected in CA1, indicating that TrkB plays fundamentally different roles in structural plasticity in these brain areas.adult cortical plasticity ͉ BDNF signaling ͉ synapse stability ͉ transgenic mice D uring development, synapse formation and elimination are regulated by molecular cues, spontaneous activity, and experience (1, 2). Most glutamatergic synapses on excitatory neurons are situated on dendritic spines. Live imaging of neurons expressing GFP has provided important information on the dynamics of spine formation and maintenance (3-8). Filopodia are short-lived fingershaped protrusions and believed to be precursors of dendritic spines (9, 10). Newly formed spines are often thin or long and appear and disappear within days. Some mature into mushroom or stubby spines, which are more stable and often persist for months (7,8). There are strong correlations between spine size, spine persistence, synaptic efficacy, and the number of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) at the postsynaptic density (8,11,12). With development and aging of the cortex, there is a shift toward larger and more persistent spine types (3,7,13).Spine dynamics are influenced by plasticity. Long-term potentiation in hippocampus is associated with an increase in spine size (14) and spine formation (15), whereas term depression is associated with spine elimination (16). Interestingly, reducing synaptic input results in an increase in spine numbers, probably due to homeostatic mechanisms (17)(18)(19).Ocular dominance plasticity in V1 is associated with initial pruning and later formation and stabilization of spines (20,21) and occurs predominantly during a critical period of development. Maturation of the extracellular matrix is a major factor in ending the critical period, probably by increasing spine and axon stability (20)(21)(22) BDNF signaling through TrkB receptors is a key player in visual plasticity (23,24). It drives the development of inhibitory innervation, an important factor in ocular dominance plasticity (25,26). BDNF is...

The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitmentSensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here the authors report that the SH3 domain of the scaffold protein PSD-95 binds a lipid signaling enzyme, PI3K-C2a, that mediates inflammatory sensitization. The results show that different types of behavioural plasticity are mediated by specific domains of PSD-95 and suggest that PI3K-C2a is a potential drug target for inflammatory pain.

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Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries.

Objectives: (1) Evaluate whether initial results from percutaneous treatment of nonunion are reproducible (2) Estimate the relative cost of percutaneous treatment of nonunion versus traditional methods.Design: Retrospective multicentre case series.Setting: Four Level 1 trauma centers.Patients/Participants: Fifty-one patients (34 men and 17 women) with a median age of 51 years (range 14-81) were treated for nonunion at a median of 10 months (range 4-212) from injury.

Background Despite advancements in primary correction of hallux valgus (HV), significant rates of reoperation remain across common techniques, with complications following primary correction up to 50% according to some studies.1 This study explored different methods of surgery currently used in treating HV recurrence specifically (for which literature on the subject has been limited), evaluating open and adapted minimally invasive surgical (MIS) primary techniques used for revision. Methods In December 2020, literature search for both open and MIS surgical techniques in HV revision was conducted using PubMed, EMBASE, and MEDLINE library databases. Results and Conclusion Of initial 143 publications, 10 were finally included for data synthesis including 273 patients and 301 feet. Out of 301 feet, 80 (26.6%) underwent revision with MIS techniques (involving distal metatarsal osteotomies). Those undergoing grouped MIS revisions had an average improvement of 38.3 in their American Orthopaedic Foot and Ankle Society score, compared to 26.8 in those using open techniques. Revision approaches using grouped MIS techniques showed a postoperative reduction in intermetatarsal angle and HV angle of 5.6 and 18.4 degrees, respectively, compared to 15.5 and 4.4 degrees, respectively, for open techniques. There are, however, limitations in the current literature on MIS techniques in revision HV surgery specifically. MIS techniques grouped did not show worse outcomes or safety concerns compared to open techniques.

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