27 research outputs found

    PU.1 controls fibroblast polarization and tissue fibrosis

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    Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs

    Forearm segmental bone defect: Successful management using the Masquelet Technique with the aid of 3D printing technology

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    : The management of forearm nonunion is challenging for orthopaedic surgeons because the forearm is a unique anatomical segment in which all the bones and structures involved embody a complex functional unit. Therefore, when treating such a complex condition, the surgeon must focus not only on bone healing but also on the restoration of the native anatomy in order to replicate the normal relationship between the bones and all the surrounding structures and thus the full function of the forearm, the elbow and the wrist. Here we report the case of a 53-year-old patient with a left forearm deformity due to an atrophic nonunion of the ulna and a malunion of the radius, which was successfully managed with the use of the Masquelet technique associated with a corrective osteotomy of the radius, performed with the aid of a 3D model

    An experimental, theoretical and numerical investigation of shape memory polymers

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    The present paper deals with the experimental analysis, constitutive modeling and numerical simulation of a class of polymers, exhibiting shape memory effects. We first present and discuss the results of an experimental traction-shrinkage campaign on semi-crystalline shape memory polymers, particularly, on low-density and high-density polyethylene-based polymers. Then, we develop a new one-dimensional phenomenological constitutive model, based on the so-called phase transition approach and formulated in a finite strain framework, in order to reproduce experimental observations. The model is treated through a numerical procedure, consisting in the replacement of the classical set of Kuhn-Tucker inequality conditions by the Fischer-Burmeister complementarity function. Numerical predictions reveal that the model is able to describe qualitative aspects of material behavior, involving both orientation and thermal retraction, as well as to predict experimental orientation processes for semi-crystalline polyethylene-based polymers with different densities

    The Dagradi-Serio-Iacono operation central pancreatectomy

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    Central pancreatectomy (CP) is a segmental pancreatic resection indicated to remove benign or low-grade malignant tumors of the isthmus and proximal part of the body of the pancreas. The main advantage of this operation compared with major resections is that it permits to spare normal pancreatic parenchyma;moreover, spleen and upper digestive and biliary tracts are saved. The description of the complete operation was reported for the first time by Dagradi and Serio in 1984 and subsequently spread worldwide by Iacono and Serio. In our opinion, it should be called the Dagradi\u2013Serio\u2013Iacono operation, by the names of the surgeons who first performed it (Dagradi and Serio), and by the names of the surgeons responsible for reporting it worldwide with precise indications (Iacono and Serio). Operation requires a midline or a bilateral subcostal incision; the lesser sac is entered through dissection of the transverse colon from the omentum or by transecting the gastrocolic ligament. The pancreatic segment harboring the lesion is then mobilized and its posterior surface carefully dissected from the splenic vein and artery. Subsequently, the pancreatic portion harboring the tumor is isolated at its superior margin from the splenic artery after the pancreas is transacted. The extent of the resection of the central segment is limited on the right by the gastroduodenal artery and on the left by the need to leave at least 5 cm of normal pancreatic remnant. The resected pancreatic specimen is sent to the pathologist for confirmation of diagnosis and to check if the resection margins are adequate. Hemostasis of the two raw surfaces is achieved with interrupted 5 or 4/0 nonabsorbable stitches. When it is not stapled, theWirsung\u2019s duct of the cephalic stump is sutured selectively with a figureof- eight nonabsorbable stitch. An end-to-end invaginated pancreaticojejunostomy is carried out with a single layer of interrupted stitches. The operation is concluded with the construction of an end-to-side jejuno-jejunostomy about 50 cm distal to the pancreatic anastomosis. Other techniques for reconstruction of the distal stump using jejunum or stomach have been described. One or two soft drains are brought out on the right side. The fluid collected from this drain is checked for amylase level on postoperative days 3, 5, and 7; if the level is low or absent, the drain is removed. Central pancreatectomy is a safe technique for benign or low malignant tumors of the pancreatic neck that allows curing the tumor with evident functional results without increasing the risk for the patient. We can say that CP has a clear role like pancreaticoduodenectomy and distal pancreatectomy and we think that a pancreatic surgeon has to include this procedure in his/her technical skills. In order to obtain excellent results, correct indications and experience in pancreatic surgery are recommended

    The function of ncRNAs in rheumatic diseases

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