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The presymptomatic brain changes of granulin (GRN) disease, preceding by years frontotemporal dementia, has not been fully characterized. New approaches focus on the spatial chronnectome can capture both spatial network configurations and their dynamic changes over time. To investigate the spatial dynamics in 141 presymptomatic GRN mutation carriers and 282 noncarriers from the Genetic Frontotemporal dementia research Initiative cohort. We considered time-varying patterns of the default mode network, the language network, and the salience network, each summarized into 4 distinct recurring spatial configurations. Dwell time (DT) (the time each individual spends in each spatial state of each network), fractional occupacy (FO) (the total percentage of time spent by each individual in a state of a specific network) and total transition number (the total number of transitions performed by each individual in a specifict state) were considered. Correlations between DT, FO, and transition number and estimated years from expected symptom onset (EYO) and clinical performances were assessed. Presymptomatic GRN mutation carriers spent significantly more time in those spatial states characterised by greater activation of the insula and the parietal cortices, as compared to noncarriers (p < 0.05, FDR-corrected). A significant correlation between DT and FO of these spatial states and EYO was found, the longer the time spent in the spatial states, the closer the EYO. DT and FO significantly correlated with performances at tests tapping processing speed, with worse scores associated with increased spatial states’ DT. Our results demonstrated that presymptomatic GRN disease presents a complex dynamic reorganization of brain connectivity. Change in both the spatial and temporal aspects of brain network connectivity could provide a unique glimpse into brain function and potentially allowing a more sophisticated evaluation of the earliest disease changes and the understanding of possible mechanisms in GRN disease.

Background: Propionibacterium acnes is a common pathogen in infections after shoulder surgery. Recent reports found positive Pacnes cultures in a high percentage of patients who had revision shoulder arthroplasty for ‘‘aseptic loosening’’ without any overt signs of infection. Isolation of Pacnes is difficult, and by use of conventional microbiological protocols of 48-hour incubation, a considerable proportion of patients with possible Pacnes infection may remain unidentified. We recently noted Pacnes in shoulder joint cultures in patientsundergoingprimaryshoulderreplacementforglenohumeralarthropathywithoutanysignsofinfection. Methods: We collected aspirates and biopsy specimens from 55 consecutive patients with arthritic shoulders undergoing primary joint replacement and examined them for the presence of P acnes. Special measures were taken to ensure that the specimens were carefully taken from within the joint to reduce the risk of contamination to minimal. Results: In 23 of 55 consecutive patients (41.8%) undergoing primary shoulder joint replacement, P acnes was found in the joint fluid and tissues taken before the insertion of the implants. All these patients were treated early postoperatively with pathogen-directed specific dual oral antibiotic treatment for 4 weeks. In none have any signs of infection developed. Discussion and conclusion: This finding of a high incidence of P acnes in joints before arthroplasty may suggest a role of P acnes in the pathogenesis of glenohumeral arthropathy. In addition, it raises the question of whether development of painful joint replacement later on and presumed aseptic loosening do, in fact, comprise an unrecognized low-grade infection that has been present since before the index operation. Level of evidence: Level IV, Case Series, Prognosis Study. 2013 Journal of Shoulder and Elbow Surgery Board of Trustees.