The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.

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The extracellular matrix is an intricate and essential network of proteins and non-proteinaceous components that provide a conducive microenvironment for cells to regulate cell function, differentiation, and survival. Fibronectin is one key component in the extracellular matrix that participates in determining cell fate and function crucial for normal vertebrate development. Fibronectin undergoes time dependent expression patterns during stem cell differentiation, providing a unique stem cell niche. Mutations in fibronectin have been recently identified to cause a rare form of skeletal dysplasia with scoliosis and abnormal growth plates. Even though fibronectin has been extensively analyzed in developmental processes, the functional role and importance of this protein and its various isoforms in skeletal development remains less understood. This review attempts to provide a concise and critical overview of the role of fibronectin isoforms in cartilage and bone physiology and associated pathologies. This will facilitate a better understanding of the possible mechanisms through which fibronectin exerts its regulatory role on cellular differentiation during skeletal development. The review discusses the consequences of mutations in fibronectin leading to corner fracture type spondylometaphyseal dysplasia and presents a new outlook towards matrix-mediated molecular pathways in relation to therapeutic and clinical relevance.

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Objectives To carry out a real-life retrospective, multicenter survey on the prevalence, subtype, and proposed treatments of premature ejaculation in China. Methods Real-life data were provided by 8 major Centers from China, selected as active in basic and clinical research on PE and participating to international meetings of sexual medicine and andrology. Centers provided a filled survey containing relevant information concerning PE prevalence, pathogenesis and treatment. Results In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by Traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: while the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. Conclusions Taking switching rates as surrogate markers of treatment failure, this real-life study – the largest in the field - shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies. Conflicts of Interest EAJ is or has been a speaker and/or paid consultant for Bayer, Ibsa, Lundbeck, Menarini, Merk-Serono, Otsuka, Pfizer, Shionogi, and Viatris. AS has been a paid consultant for Menarini. All others declare not to have any competing interest for the present manuscript.