Glial cells undergo rapid changes following acute chemogenetic manipulation of cortical layer 5 projection neurons

Bidirectional communication between neurons and glial cells is crucial to establishing and maintaining normal brain function. Some of these interactions are activity-dependent, yet it remains largely unexplored how acute changes in neuronal activity affect glial-to-neuron and neuron-to-glial dynamics. Here, we use excitatory and inhibitory designer receptors exclusively activated by designer drugs (DREADD) to study the effects of acute chemogenetic manipulations of a subpopulation of layer 5 cortical projection and dentate gyrus neurons in adult (Rbp4Cre) mouse brains. We show that acute chemogenetic neuronal activation reduces synaptic density, and increases microglia and astrocyte reactivity, but does not affect parvalbumin (PV+) neurons, only perineuronal nets (PNN). Conversely, acute silencing increases synaptic density and decreases glial reactivity. We show fast glial response upon clozapine-N-oxide (CNO) administration in cortical and subcortical regions. Together, our work provides evidence of fast, activity-dependent, bidirectional interactions between neurons and glial cells

Scanning the landscape: ECFS Clinical Trial Network: CT imaging monitoring strategies

ObjectivesThere is heterogeneity in the practice of computed tomography (CT) imaging across European cystic fibrosis (CF) centres. The European Cystic Fibrosis Society – Clinical Trial Network (ECFS-CTN) Imaging Standardisation Working Group surveyed CTN sites and respiratory research colleagues (from the European Respiratory Society) to assess current CT imaging practice, promote standardisation and sharing of knowledge. The key project objectives are to seek European consensus on CT imaging applications and develop European recommendations.Methods4 surveys of ECFS CTN sites and European Respiratory Society colleagues were conducted in 2022/3 using a popular online survey platform. These assessed (1) paediatric, (2) adult applications of CT imaging strategies, (3) Low dose CT and (4) MRI practices. This abstract represents the output of the CT imaging strategies surveys which laid the foundation for a current 3-round Delphi process, to seek consensus for the development of European recommendations.ResultsThe CT imaging strategies surveys n = 65 (n = 43 paediatric; n = 22 adult centre specialists) assessed practice regarding irradiation dose, early structural lung disease, indications, timing and frequency of CT imaging, scan reporting, special indications; treatment response and future perspectives of CT in CF treatment and research. Paediatric centre results reported primary use of CT imaging in CF for tracking of structural lung disease progression. Adult centres reported most frequent use for evaluation of nontuberculous mycobacterium and Aspergillosis infections, haemoptysis and pneumothoraces. The current Delphi process (n = 25 statements) is aiming for completion and recommendations to be available by summer 2024.ConclusionsThe CT Monitoring Strategies group is currently completing international guidance to promote standardisation of CT imaging in CF, including harmonisation of CT parameters and key recommendations for research and clinical application.<br/

Treatment compliance in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection treated with tobramycin inhalation powder : The FREE study

Background: A high treatment burden with nebulised therapies in cystic fibrosis (CF) patients is the major limitation for treatment compliance; moreover, studies on treatment compliance with inhaled antibiotics are limited. This study assessed compliance to TOBI\uae Podhaler\u2122 (TIP) treatment in CF patients with chronic Pseudomonas aeruginosa (Pa) infections in a real-world setting using the Italian Treatment Adherence CF Questionnaire (ITA-CFq). Methods: This longitudinal, multicentre, cohort study included 2 follow-up (FU) visits: FU-1 at 3-months\ub115-days from the baseline visit and FU-2 at the end of third TIP cycle (or 6-months after enrolment, whichever occurred first). The effect of TIP on quality-of-life (QoL) and treatment satisfaction were evaluated using Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Treatment Satisfaction Questionnaire for Medication (TSQM), respectively. Overall compliance to treatments was assessed using ITA-CFq. Results: Eighty-two patients (mean age, 24.8 \ub1 7.9 years), including 22 paediatric patients (age, <18 years), were enrolled in the study; 56 (68.3%) patients, including 17 paediatric patients, completed the study. At baseline, the mean compliance score to aerosol antibiotic treatment was 7.8 \ub1 3.2; upon introducing TIP, the compliance score improved to 9.4 \ub1 1.2 at the FU-1 and thereafter remained stable at 9.5 \ub1 1.2. TSQM was higher for the convenience domain (74.2 \ub1 17.1 at enrolment and slightly improved to 77.8 \ub1 15.9 at FU-2) following TIP initiation. No substantial effect of TIP was observed on the QoL when measured using the revised CFQ-R. The safety profile was in line with previous findings. Conclusion: TIP was convenient to use and led to improved treatment adherence in CF patients with chronic Pa-infection