Presse Med
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Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by variants in the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR dysfunction results in abnormal chloride and bicarbonate transport in epithelial cells, leading to a multiorgan disease dominated by respiratory and digestive manifestations. The respiratory disease, which is characterized by airway mucus plugging, chronic bacterial infection and progressive development of bronchiectasis, may lead to chronic respiratory failure, which is the main cause of premature death in people with CF. ⋯ Although an increasing proportion of people with CF are being treated with CFTR modulators, challenges remain regarding access to CFTR modulators due to their high cost, and their lack of marketing approval and/or effectiveness in people with rare CFTR variants. The anticipated increase in the number of adults with CF and their aging also challenge the current organization of CF care. The purpose of this review article is to describe current status and future perspective of CF disease and care.
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Bronchiectasis is a final common pathway of a wide variety of underlying conditions including infectious, autoimmune, allergic, genetic and inflammatory conditions. Patients experience a chronic disease with variable clinical symptoms and course, but most experience cough, sputum production and recurrent exacerbations. Symptoms of bronchiectasis lead to poor quality of life and exacerbations are the major driver of morbidity and mortality. ⋯ Airway clearance is the mainstay of therapy for patients with symptoms of cough and sputum production. Frequently exacerbating patients may benefit from long term antibiotic or mucoactive therapies. Bronchiectasis is a heterogeneous disease and increasingly precision medicine approaches are advocated to target treatments most appropriately and to limit the emergence of antimicrobial resistance.
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The 'mesocircuit hypothesis' proposes mechanisms underlying the recovery of consciousness following severe brain injuries. The model builds up from a single premise that multifocal brain injuries resulting in coma and subsequent disorders of consciousness produce widespread neuronal death and dysfunction. Considering the general properties of cortical, thalamic, and striatal neurons, a lawful and specific circuit-level mechanism is constructed based on these known anatomical and physiological specializations of neuronal subtypes. ⋯ Many studies have examined predictions of the mesocircuit model; here we first present the model and review the accumulated evidence for several predictions of model across multiple stages of recovery function in human subjects. Recent studies linking the mesocircuit model, the ABCD model, and interactions with the frontoparietal network are reviewed. Finally, theoretical implications of the mesocircuit model at the neuronal level are considered to interpret recent studies of deep brain stimulation in the central lateral thalamus in patients recovering from coma and in new experimental models in the context of emerging understanding of neuronal and local circuit mechanisms underlying conscious brain states.