FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light-based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell-instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick-based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native-like mechanical properties is demonstrated

Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering

Articular cartilage defects caused by traumatic injury rarely heal spontaneously and predispose into post-traumatic osteoarthritis. In the current autologous cell-based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout of TGF-β-activated kinase 1 (TAK1) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro-inflammatory and catabolic NF-κB pathway. The TAK1-KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro-inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the TAK1-KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm-shift for the creation of more potent and functional tissues for use in regenerative medicine

Projeto básico do Programa Esporte e Lazer da Cidade - Liga Municipal de Futebol Suiço e Desporto de Ponta Grossa

O documento integra o acervo institucional do Programa Esporte e Lazer da Cidade/Vida Saudável/Ministério do Esporte.Projeto básico para renovação do Convênio do Ministério do Esporte com a Prefeitura Municipal de Ponta Grossa, PR, para núcleo do Programa Esporte e Lazer da Cidade, na modalidade urbana - todas as faixas etárias. Contem: dados de identificação do projeto e da entidade, dirigente, coordenador técnico, entidade de controle social, apresentação, justificativa, comunidade atendida, dados do município, parcerias, metas, atividades, eventos, formação, divulgação e inscrições, núcleos, itens solicitados do Programa Pintando a Liberdade, cadastro da classificação, cadastro de materiais e contrapartida.DoaçãoPELC e Vida Saudáve

Engineering of the endogenous HBD promoter increases HbA2

The β-hemoglobinopathies, such as sickle cell disease and β-thalassemia, are one of the most common genetic diseases worldwide and are caused by mutations affecting the structure or production of β-globin subunits in adult hemoglobin. Many gene editing efforts to treat the β-hemoglobinopathies attempt to correct β-globin mutations or increase γ-globin for fetal hemoglobin production. δ-globin, the subunit of adult hemoglobin A2, has high homology to β-globin and is already pan-cellularly expressed at low levels in adult red blood cells. However, upregulation of δ-globin is a relatively unexplored avenue to increase the amount of functional hemoglobin. Here, we use CRISPR-Cas9 to repair non-functional transcriptional elements in the endogenous promoter region of δ-globin to increase overall expression of adult hemoglobin 2 (HbA2). We find that insertion of a KLF1 site alone is insufficient to upregulate δ-globin. Instead, multiple transcription factor elements are necessary for robust upregulation of δ-globin from the endogenous locus. Promoter edited HUDEP-2 immortalized erythroid progenitor cells exhibit striking increases of HBD transcript, from less than 5% to over 20% of total β-like globins in clonal populations. Edited CD34 +hematopoietic stem and progenitors (HSPCs) differentiated to primary human erythroblasts express up to 46% HBD in clonal populations. These findings add mechanistic insight to globin gene regulation and offer a new therapeutic avenue to treat β-hemoglobinopathies.ISSN:2050-084

Projeto básico do Programa Esporte e Lazer da Cidade - Liga Municipal de Futebol Suiço e Desporto de Ponta Grossa

O documento integra o acervo institucional do Programa Esporte e Lazer da Cidade/Vida Saudável/Ministério do Esporte.Projeto básico para renovação do Convênio do Ministério do Esporte com a Prefeitura Municipal de Ponta Grossa, PR, para núcleo do Programa Esporte e Lazer da Cidade, na modalidade urbana - todas as faixas etárias. Contem: dados de identificação do projeto e da entidade, dirigente, coordenador técnico, entidade de controle social, apresentação, justificativa, comunidade atendida, dados do município, parcerias, metas, atividades, eventos, formação, divulgação e inscrições, núcleos, itens solicitados do Programa Pintando a Liberdade, cadastro da classificação, cadastro de materiais e contrapartida.DoaçãoPELC e Vida Saudáve

Projeto básico do Programa Esporte e Lazer da Cidade - Liga Municipal de Futebol Suiço e Desportos de Ponta Grossa

O documento integra o acervo institucional do Programa Esporte e Lazer da Cidade/Vida Saudável/Ministério do Esporte.Projeto básico para renovação do Convênio do Ministério do Esporte com a Prefeitura Municipal de Ponta Grossa, PR, para núcleo do Programa Esporte e Lazer da Cidade, na modalidade urbana - todas as faixas etárias. Contem: dados de identificação do projeto e da entidade, dirigente, coordenador técnico, entidade de controle social, apresentação, justificativa, comunidade atendida, dados do município, parcerias, metas, atividades, eventos, formação, divulgação e inscrições, núcleos, itens solicitados do Programa Pintando a Liberdade, cadastro da classificação, cadastro de materiais e contrapartida.DoaçãoPELC e Vida Saudáve

Real-time three-dimensional transesophageal echocardiography : improvements in intraoperative mitral valve imaging

Background: Successful surgical repair of a regurgitant mitral valve (MV) is dependent on a comprehensive assessment of its complex anatomy. Although there is limited evidence of the feasibility and accuracy of intraoperative real-time 3-dimensional transesophageal echocardiography (RT3DTEE) in MV surgery, its use is increasing worldwide. We designed this prospective observational study of patients with mitral regurgitation to test initial findings on the accuracy of RT3DTEE images in the diagnosis of MV prolapse and chordal rupture relative to 2D imaging and to assess the potential of RT3DTEE for visualizing leaflet clefts. Methods: TEE-certified anesthesiologists examined 62 consecutive patients undergoing MV surgery by acquiring a full standard set of 2D TEE sections and 3D zoom recordings. Offline, 2D and 3D images were presented independently and in randomized order to 2 expert interpreters. Accuracy was determined using the surgical findings as the “gold standard.” Results: Surgical inspection identified 52 cases of MV prolapse (MVP). RT3DTEE correlated stronger with the surgical findings than 2D TEE for detection and localization of MVP (difference in proportions = 33.9%, P < 0.001) and chordal rupture (difference in proportions = 25.8%, P < 0.001). The superiority of RT3DTEE was significant for scallops A2, P1, P2 in MVP and A2, P2 in chordal rupture (all P < 0.05). In 22 patients, leaflet clefts were also surgically repaired, and RT3DTEE was feasible in accessing them (κ = 0.65, confidence interval [0.44, 0.81]). Conclusion: Although 2D TEE is currently the standard tool for intraoperative imaging in MV surgery, RT3DTEE improves the visualization of MV pathology and increases the accuracy of interpretation by facilitating spatial orientation. Further investigations, particularly those aimed at establishing its cost effectiveness, are indicated

Engineering Inflammation-Resistant Cartilage : Bridging Gene Therapy and Tissue Engineering

Articular cartilage defects caused by traumatic injury rarely heal spontaneously and predispose into post-traumatic osteoarthritis. In the current autologous cell-based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout of TGF-beta-activated kinase 1 (TAK1) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro-inflammatory and catabolic NF-kappa B pathway. The TAK1-KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro-inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the TAK1-KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm-shift for the creation of more potent and functional tissues for use in regenerative medicine.Peer reviewe

Un monastero sul mare

The remains of the monastery of San Quirico stand on the slopes of Poggio Tondo, a hill not far from the ancient city of Populonia. They overlook the Tyrrhenian Sea, dotted with the islands of the Tuscan archipelago. Field research at this site, carried out in the first decade of the new millennium by two different teams, from Siena University and Venice’s Ca’ Foscari University, respectively, was part of ongoing efforts to expand the Baratti-Populonia Archeological Park, and to further explore the features present within it. This volume contains the results of this research work: a scientific publication of the excavation, and a critical analysis of the material found. Processing of the data collected during these investigations, together with a re-reading of written documentation, has made it possible to piece together the complex history of this important monastery, in a totally new narration. In this narration, the history of the monastery, and of the features which existed prior to it, are closely interwoven with the history of the promontory of Populonia and the surrounding area, ultimately producing a new overview which sets out the historical boundaries of this area, between Late Antiquity and the modern era.I resti del monastero di San Quirico si trovano sulle pendici del poggio Tondo, a poca distanza dall’antica città di Populonia, rivolti verso lo specchio del mare Tirreno costellato dalle isole dell’arcipelago toscano. Le ricerche archeologiche in questo sito, realizzate nel primo decennio del nuovo millennio da due differenti équipe, rispettivamente dell’Università di Siena e Ca’ Foscari di Venezia, si sono svolte nell’ambito degli interventi di ampliamento e di valorizzazione del parco archeologico di Baratti-Populonia. Questo volume contiene i risultati di quelle ricerche: l’edizione scientifica dello scavo e l’analisi critica dei materiali rinvenuti. La rielaborazione dei dati raccolti durante tali indagini, unita ad una rilettura della documentazione scritta, ha poi permesso di ricomporre le complesse vicende di questo importante monastero, in una nuova ed inedita narrazione. In tale narrazione le vicende del cenobio e delle sue preesistenze si intrecciano con quelle del promontorio di Populonia e dei territori limitrofi fino a delineare un quadro di sintesi che ridisegna i confini storici di questo territorio tra la Tarda Antichità e l’Età Moderna

Sexuality in women with endometriosis: a critical narrative review

Endometriosis is a chronic gynecological disease that generally affects young and sexually active women in different stages of their development and sexual life. Because endometriosis affects about 5-10% of women in reproductive age, it is possible to estimate that about 2-4% of those who are sexually active may suffer from sexual dysfunction caused by this disease. Surgical and pharmacological treatments of endometriosis can improve the patient's sexual function in the medium and long term, but not necessarily lead to a definitive resolution of the sexual issue. For this reason, the ideal treatment should be conducted by a multidisciplinary team, with the aim to improve overall sexual functioning and not only to reduce the painful symptoms during intercourse. In light of these considerations, the aim of this narrative review was to provide a general overview about the impact of endometriosis on sexuality of women affected and the effectiveness of surgical and pharmacological treatments in improving sexual function