Adipose-Derived Stem Cells in Bone Tissue Engineering: Useful Tools with New Applications

Adipose stem cells (ASCs) are a crucial element in bone tissue engineering (BTE). They are easy to harvest and isolate, and they are available in significative quantities, thus offering a feasible and valid alternative to other sources of mesenchymal stem cells (MSCs), like bone marrow. Together with an advantageous proliferative and differentiative profile, they also offer a high paracrine activity through the secretion of several bioactive molecules (such as growth factors and miRNAs) via a sustained exosomal release which can exert efficient conditioning on the surrounding microenvironment. BTE relies on three key elements: (1) scaffold, (2) osteoprogenitor cells, and (3) bioactive factors. These elements have been thoroughly investigated over the years. The use of ASCs has offered significative new advancements in the efficacy of each of these elements. Notably, the phenotypic study of ASCs allowed discovering cell subpopulations, which have enhanced osteogenic and vasculogenic capacity. ASCs favored a better vascularization and integration of the scaffolds, while improvements in scaffolds' materials and design tried to exploit the osteogenic features of ASCs, thus reducing the need for external bioactive factors. At the same time, ASCs proved to be an incredible source of bioactive, proosteogenic factors that are released through their abundant exosome secretion. ASC exosomes can exert significant paracrine effects in the surroundings, even in the absence of the primary cells. These paracrine signals recruit progenitor cells from the host tissues and enhance regeneration. In this review, we will focus on the recent discoveries which have involved the use of ASCs in BTE. In particular, we are going to analyze the different ASCs' subpopulations, the interaction between ASCs and scaffolds, and the bioactive factors which are secreted by ASCs or can induce their osteogenic commitment. All these advancements are ultimately intended for a faster translational and clinical application of BTE

Editorial: Chasing brain dynamics at their speed: what can time-varying functional connectivity tell us about brain function?

In the past decades, the growing field of network neuroscience has opened new perspectives on the study of the brain and its function. The integration of tools from network analysis and system neuroscience has allowed researchers to explore the properties of brain networks, offering a valuable alternative to traditional methods based on simple subtraction and mass univariate analysis (Sporns, 2010; Behrens and Sporns, 2012). This has led to an exponential growth of connectivity algorithms and methods designed to capture the intrinsic dynamics of human brain networks, both at rest and during active tasks. As a result, a new research direction has emerged. The quantification of spatio-temporal dynamics of functional connectivity (FC) is offering new means to observe a vast repertoire of brain functions. Despite significant advances in this domain, there are still major challenges to address. This is partly due to the rapid and distributed nature of brain interactions, with large-scale networks that constantly evolve and coordinate activity to produce human perception, cognition, and behavior at sub-second timescales. Additionally, brain network activity can vary widely within and across individuals (Finn et al., 2015; Van De Ville et al., 2021), as well as in clinical conditions and brain disorders (see Miao et al.). Thus, modeling whole-brain network dynamics, accounting for the necessary spatial and temporal resolution at both individual and population levels, remains a crucial goal yet to be fully achieved. The present Research Topic contains a collection of methodological and empirical studies that touch upon some of the main challenges in the field, collectively providing insight into the current state of research and the potential solutions for advancing the field of dynamic network neuroscience in the future

Evaluation of analytical performance of a novel immunoenzymometric assay for cTnI

Letter to the Editor. We evaluated the analytical performance of the immunoenzymometric assay for the cTnI, named ST AIA-PACK cTnI 3rd-Gen, using the automated AIA-2000 platform (Tosoh Corporation, Tokyo, Japan). This method is a two-site immunoenzymometric assay, which uses a combination of two monoclonal antibodies, respectively directed to 41–49 and 87–91 amino acids of the cTnI peptide chain, and the ternary troponin ITC complex as a calibration antigen [1]

Eleonora d'Aragona e la costruzione di un "corpo" politico al femminile (1450-1493)

La investigación se ha centrado en la biografía de Leonor de Aragón, hija del rey Ferrante de Nápoles y mujer de Hércules de Este. En una perspectiva más amplia que la tradicional cronología, se estudiará la ideología de la dinastía Trastámara de Nápoles y la historia política y cultural de la Italia renacentista. La tipología de las fuentes utilizadas – diplomáticas y epistolares – ha permitido combinar diversos niveles de análisis: biográfico, ideológico, de género, político y social. El estudio apunta a evidenciar, en primer lugar, el papel político de Leonor en el gobierno del ducado estense: un ejercicio concreto de un poder – declinado en formas diversas – que se persigue sobre todo a través del copioso e inédito intercambio epistolar entre la duquesa y Hércules, al hilo de las frecuentes ausencias del duque. En segundo lugar, gracias a la correspondencia entre Leonor y su padre, se apunta a la conformidad ideológica con una tradición familiar. Este trabajo tiende además a demostrar cómo la duquesa, en cuanto mujer de poder, fue el resultado de un proyecto formativo aragonés dirigido tanto a la descendencia masculina como a la femenina. <br /

Gestão de Pessoas e Ações de Prevenção Do Assédio Moral: Os Casos de Duas Cooperativas Agropecuárias Do Paraná

The objective of this study was to identify and analyze how preventive work is done on issues related to moral harassment in two agricultural cooperatives in Paraná. The locus chosen for analysis was justified by the need for actions that curb harassment in organizations and by the peculiarity of the environment, in addition to the two cooperatives surveyed being large employers in their region. A qualitative case study approach was taken. Descriptive data was collected through document research and interviews with four managers of the two cooperatives. Findings revealed that both cooperatives analyzed have no records of moral harassment in the Regional Labor Court and use some prevention methods. In addition, statements by personnel management professionals presented some discrepancies with other professionals interviewed, which may be related to a lack of knowledge on the theme or to cultural aspects. The Green Cooperative presented more preventive methods to moral harassment than the Blue Cooperative, including a code of ethics, denunciations via e-mail, organization environment research, a denunciation box and harassment prevention training for future leaders. The Blue Cooperative uses formal channels of communication and employee dialogue, but nothing specifically directed towards situations of harassment, organization climate research, or a code of ethics. Areas of personnel management are suggested to invest more in communicating prevention actions with those involved, which encourages dialogue and the dissemination of knowledge on what harassment is and how to prevent it.Este estudo tem como objetivo identificar e analisar como são trabalhadas preventivamente as questões relativas ao assédio moral em duas cooperativas agropecuárias do Paraná. O lócus escolhido para análise justificou-se pela necessidade de ações que coíbam o assédio moral nas organizações e na peculiaridade do ambiente, além das duas cooperativas pesquisadas serem grandes empregadoras da sua região. A abordagem foi qualitativa, do tipo estudo de casos, a pesquisa foi do tipo descritiva com coleta de dados por meio de pesquisa documental e entrevista com quatro gestores de duas cooperativas paranaenses. Como resultados, a pesquisa revelou que as duas cooperativas analisadas não possuem nenhum registro de assédio moral no Tribunal Regional do Trabalho, que elas utilizam alguns métodos de prevenção ao assédio moral e que os discursos dos profissionais de Recursos Humanos apresentam algumas discrepâncias dos outros profissionais entrevistados. A Cooperativa Verde apresentou mais métodos preventivos ao assédio moral que a Cooperativa Azul, dentre eles estão o código de ética, denúncias via email, pesquisa de clima organizacional, caixa para denuncias e treinamento para futuros líderes abordando o tema do assédio. A Cooperativa Azul utiliza os canais formais de comunicação e diálogo com os funcionários, mas nada voltado diretamente para situações de assédio, pesquisa de clima organizacional, e código de ética. Sugere-se que as áreas de gestão de pessoas invistam mais na comunicação das ações de prevenção junto aos envolvidos, incentivando o diálogo e a disseminação do conhecimento sobre o que vem a ser o assédio e suas formas de prevenção

Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NFkB/Rel- specific decoy oligodeoxynucleotides

The activity of NF-kB/Rel nuclear factors is known to inhibit apoptosis in various cell types. We investigated whether the subtraction of NF-kB/Rel activity influenced the response of 11 AML (M1, M2 and M4) patients’ cells to AraC. To this end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide (ODN) carrying the NF-kB/Rel- consensus sequence. Cell incubation with this ODN, but not its mutated (scrambled) form used as a control, resulted in abating the NF-kB/Rel nuclear levels in these cells, as verified by electrophoretic mobility shift assay (EMSA) of cells’ nuclear extracts. We incubated the leukemic cells with AraC (32 or 1 mM), in either the absence or presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The spontaneous cell apoptosis detectable in the absence of AraC (,25%) was not modulated by the oligonucleotide presence in cell cultures. On the other hand, in 10 of the 11 samples tested, the decoy kB, but not the scrambled ODN significantly (P ,0.01 in a Student’s t test) enhanced cell apoptotic response to AraC. Such an effect was particularly remarkable at low AraC doses (1 mM). These findings indicate that NF-kB/Rel activity influences response to AraC in human primary myeloblastic cells, and suggests that the inhibition of NF-kB/Rel factors can improve the effect of chemotherapy in AM

Thrombotic complications in adult patients with lymphoma: A meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events

Thrombotic complications in hematologic malignancies have important clinical implications. In this meta-analysis we sought to obtain accurate estimates of the thrombotic risk in lymphoma patients. Articles were searched in electronic databases and references. Eighteen articles were identified (29 cohorts, 18 018 patients and 1149 events). Pooled incidence rates (IRs) were calculated by the use of a method based on the exact maximum likelihood binomial distribution. The global IR of thrombosis was 6.4% (95% confidence interval [CI] 6.0%-6.8%). The global IRs of venous or arterial events were 5.3% (95% CI, 5.0%-5.7%) and 1.1% (95% CI, 0.9%-1.2%), respectively. The IR of thrombosis observed in subjects with non-Hodgkin lymphoma (NHL) was 6.5% (95% CI, 6.1%-6.9%), significantly greater than that observed for patients with Hodgkin lymphoma (4.7%; 95% CI, 3.9%-5.6%). Within NHL, patients with high-grade disease had a greater risk of events (IR 8.3%; 95% CI, 7.0%-9.9%) than low-grade disease (IR 6.3%; 95% CI, 4.5%-8.9%). This meta-analysis shows that the IR of thrombosis in lymphoma patients is quite high, especially in those with NHL at an advanced stage of the disease. These results may help better defining lymphoma populations at high thrombotic risk, to whom prophylactic approaches could be preferentially applied.Fil: Caruso, Vanesa. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Di Castelnuovo, Augusto. Università Cattolica del Sacro Cuore; ItaliaFil: Meschengieser, Susana. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Lazzari, María Ángela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: De Gaetano, Giovanni. Università Cattolica del Sacro Cuore; ItaliaFil: Storti, Sergio. Università Cattolica del Sacro Cuore; ItaliaFil: Iacoviello, Licia. Università Cattolica del Sacro Cuore; ItaliaFil: Donati, Maria Benedetta. Università Cattolica del Sacro Cuore; Itali

Combined Modality Treatment Including Methotrexate-Based Chemotherapy For Primary CENTRAL Nervous System Lymphoma: A Single Institution Experience

Chemotherapy including high-dose methotrexate (HD-MTX), with or without radiotherapy, is standard treatment for primary central nervous system lymphoma (PCNSL). It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m2 for 2 cycles) prior to whole brain radiotherapy (WBRT). In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC) (2g/m2 for 4 doses for 2 cycles). Complete remission at the end of the combined treatment was obtained in 23 of 34 assessable patients (67%), and the predicted 5-year overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77%) patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted

Protein and Crude Fiber Levels in the Diet of Juvenile Matrinxã, Brycon cephalus, an Amazonian Fish

The results of an experiment with matrinchã, Brycon cephalus,fed 9 diets, combined in 3 levels of protein (19, 25 e 31 %) and 3 levels of fiber (ca. 2, 10 and 20%), are shown. The final weight was positivelly influenced when fish fed higher levels of protein, but was not influenced by fiber levels. The higher levels of protein in the diet, increased protein content of carcass, and decreased the content of fat and ash, while fish fed the highest fiber levels assimilated more protein, had a higher percentage of ash and a lower fat content in the body composition. The results indicated that ingredients with high levels of fiber are well assimilated by matrinchã, increasing this way the range of agricultural by-products, normally rich in fiber, that could be used to formulate practical diets for this specie.São apresentados os resultados de um experimento realizado com matrinxãs, Brycon cephalus,alimentados com nove dietas contendo três níveis de proteína (19, 25 e 31%) combinados com três níveis de fibra (cerca de 2, 10 e 20%). O peso final foi mais elevado para os peixes que receberam ração com maiores níveis de proteína bruta, mas não foi afetado pela elevação dos níveis de fibra bruta. Os níveis mais elevados de proteína na ração aumentaram o conteúdo de proteína da carcaça, e diminuíram o conteúdo de gordura e cinza, enquanto os peixes alimentados com as rações com os níveis mais elevados de fibra tinham mais proteína e cinza corporal e menores níveis de gordura. Os resultados sugerem que ingredientes com níveis elevados de fibra são bem utilizados pelo matrinxã, aumentando desta maneira a variedade de subprodutos agrícolas, normalmente ricos em fibra bruta, que podem ser usados na formulação de dietas práticas para esta espécie