Estudio experimental comparativo de la estabilidad de distintos tutores externos

Se investigó la rigidez de 11 diferentes montajes de tutores externos usando un modelo experimental con tibias cadavéricas a las cuales se realizaba una osteotomía transversal mediodiafisaria perpendicular al eje longitudinal del hueso, creando entre ambos segmentos una brecha de 35 mm, simulando una fractura. Mediante dispositivos de medición diseñados y construidos especialmente para este estudio se logró cuantificar los desplazamientos que se producen en el foco de fractura ante cargas de compresión axial, torsión y flexiones anteroposterior y mediolateral. Se determinó en cada ensayo la carga segura y carga máxima previamente definidas. La mayor rigidez a la compresión axial se observó en el tutor Orthofix a la torsión y a la flexión anteroposterior en el Kronner biplanar y a la flexión mediolateral en el tutor AO triangulado. Se determina la rigidez total porcentual de cada montaje como índice que representa el funcionamiento promedio del mismo en todas las modalidades de carga. Se consideran las indicaciones, ventajas, complicaciones y fundamentalmente la biología de la consolidación ósea en referencia a los fijadores externos. Se concluye sobre el cuidado con que debe ser conducida la carga de un miembro con fractura inestable, ya que la mayoría de los montajes permiten más de 1 mm de movimiento en la brecha de la fractura con una carga axial baja.The stiffness of 11 different device configurations of external fixation was investigated in an experimental model using human cadaveric tibia. After application of the different devices, a diaphyseal osteotomy allowing removal of a 35 mm bone segment was performed in the specimens. Displacements of the bone fragments at the osteotomy site induced by compresion loading, torsion, and both anteroposterior and mediolateral flexion were measured with dispositives designed for this experiment. Maximal load and that required for inducing 1 mm displacement were recorded. The higher stiffness corresponded to the Orthofix fixator in axial compression, the Kronner biplanar device in anteroposterior flexion, and the triangular configuration of the AO device in mediolateral flexion. A total stiffness index of each configuration as an average of the behavior against all loading modahties was obtained. The indications, advantages, complications and the biology of bone consolidation wien regards to external fixation are considered. As conclusion, progressive loading of the extremity with unstable fracture requires a close monitorization, since most of the device configurations analyzed allow more than 1 mm displacement of bone fragments at the fracture site, even with low axial loading

PGE2-Induced IDO1 Inhibits the Capacity of Fully Mature DCs to Elicit an In Vitro Antileukemic Immune Response.

In the last years, dendritic cells (DC) have been evaluated for antitumor vaccination. Although DC-based vaccines have raised great expectations, their clinical translation has been largely disappointing. For these results, several explanations have been proposed. In particular, the concomitant expression by DCs of tolerogenic pathways, such as the immunosuppressive agent indoleamine 2,3-dioxygenase-1 (IDO1), has been demonstrated. The aim of this study is to evaluate both the stimulatory and the tolerogenic feature of monocyte-derived DCs (Mo-DCs) after maturation with PGE2. In particular, the role of IDO1 expression in PGE2-matured Mo-DCs has been addressed. Here we show that PGE2, which is required for full maturation of DCs, is one mediator of DC tolerance by enhancing IDO1. PGE2-mediated expression of IDO1 results in the production of kynurenine, in the generation of Tregs, and in the inhibition of either the allogeneic or the autologous antigen-specific stimulatory capacity of DCs. When pulsed with leukemic lysates and matured with PGE2, DCs are impaired in the induction of IFN-γ secreting CD4(+) and CD8(+) T cells due to IDO1 upregulation. Moreover, the inhibition of IDO1 enhances the antileukemic response. Overall, these results point toward the use of IDO1 inhibitors to enhance the vaccination capacity of DCs, matured with PGE2

Characterization of symbolic play in deaf children: case and control studies

BACKGROUND: children with hearing loss do not acquire language at the same time nor at the same rate of normal hearing children because the learning process of oral language is essentially auditory. Child development consists in gradually acquiring motor and psychocognitive abilities. Entering the symbolic world is decisive for the child to reach higher levels of linguistic complexity. AIM: to correlate symbolic play and aspects of child development in deaf children and in hearing children. METHOD: participants of this study were 32 children, of both genders, with ages between 2 and 6 years, age matched. All participants were submitted to the Evaluation of Symbolic Maturation and to the Denver Developmental Screening Test II. Sixteen participants presented moderate to profound sensory-neural hearing loss and composed the research group (RG); the remaining 16 children had normal hearing and composed the control group (CG). RESULTS: symbolism was observed in the play of 81.25% of RG and in 87.5% of CG. In the Denver Developmental Screening Test II, 100% of the RG was classified as being at risk. As for the CG, 94% of the children were classified as normal and the remaining 6% as being at risk (p<0.001). CONCLUSION: a similar performance was observed between the groups for symbolic play. However, in a qualitative analysis, the RG presented less complex symbolic play than the CG. It was observed that the RG presented a performance in the symbolic play compatible to its performance in aspects of personal-social, refined motor and gross motor control in the Denver Developmental Screening Test II.TEMA: crianças deficientes auditivas não adquirem linguagem no mesmo período e velocidade de uma criança normo-ouvinte, pois o aprendizado da linguagem oral é um evento essencialmente auditivo. O desenvolvimento da criança consiste na aquisição progressiva de habilidades motoras e psicocognitivas, e a entrada no mundo simbólico é fator preponderante para que a criança possa atingir os níveis de maior complexidade no domínio da linguagem. OBJETIVO: relacionar o jogo simbólico e aspectos do desenvolvimento infantil em crianças deficientes auditivas com seus pares ouvintes. MÉTODO: 32 crianças, de ambos os sexos, de 2 a 6 anos de idade, pareadas por idade, foram submetidas à Avaliação da Maturidade Simbólica e ao Teste de Triagem do Desenvolvimento de Denver II, sendo 16 deficientes auditivas neurossensorial de grau moderado a profundo (grupo pesquisa - GP) e 16 normo-ouvintes (grupo controle - GC). RESULTADOS: observou-se simbolismo na brincadeira de 81,25% do GP, enquanto que no GC isto ocorreu em 87,5%. No Teste de Denver II 100% do GP foi classificado como risco, e o GC apresentou 94% de crianças normais e 6% de risco (p < 0,001). CONCLUSÃO: observou-se desempenho semelhante nos dois grupos quanto ao jogo simbólico. Entretanto, numa análise qualitativa, o GP apresentou brincadeiras menos complexas que o GC. Observou-se que o GP apresentou desempenho no jogo simbólico compatível ao seu desempenho nos aspectos pessoal-social, motor fino-adaptativo e motor grosseiro do Teste de Denver II.Universidade de São PauloCentro de Estudos da VozUniversidade Federal do Rio Grande do SulUNIFESP-EPM Departamento de Fonoaudiologia da Disciplina de Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Fonoaudiologia da Disciplina de Distúrbios da Comunicação HumanaSciEL

The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells.

Dendritic cells (DCs) are professional APCs that have a role in the initiation of adaptive immune responses and tolerance. Among the tolerogenic mechanisms, the expression of the enzyme IDO1 represents an effective tool to generate T regulatory cells. In humans, different DC subsets express IDO1, but less is known about the IDO1-related enzyme IDO2. In this study, we found a different pattern of expression and regulation between IDO1 and IDO2 in human circulating DCs. At the protein level, IDO1 is expressed only in circulating myeloid DCs (mDCs) and is modulated by PGE2, whereas IDO2 is expressed in both mDCs and plasmacytoid DCs and is not modulated by PGE2. In healthy subjects, IDO1 expression requires the presence of PGE2 and needs continuous transcription and translation, whereas IDO2 expression is constitutive, independent from suppressor of cytokine signaling 3 activity. Conversely, in patients suffering from inflammatory arthritis, circulating DCs express both IDO1 and IDO2. At the functional level, both mDCs and plasmacytoid DCs generate T regulatory cells through an IDO1/IDO2-dependent mechanism. We conclude that, in humans, whereas IDO1 provides an additional mechanism of tolerance induced by proinflammatory mediators, IDO2 is stably expressed in steady-state conditions and may contribute to the homeostatic tolerogenic capacity of DCs

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

Improved magnetic charged system search optimization algorithm with application to satellite formation flying

This paper is devoted to the implementation and application of an improved version of the metaheuristic algorithm called magnetic charged system search. Some modifications and novelties are introduced and tested. Firstly, the authors’ attempt is to develop a self-adaptive and user-friendly algorithm which can automatically set all the preliminary parameters (such as the numbers of particles, the maximum iterations number) and the internal coefficients. Indeed, some mathematical laws are proposed to set the parameters and many coefficients can dynamically change during the optimization process based on the verification of internal conditions. Secondly, some strategies are suggested to enhance the performances of the proposed algorithm. A chaotic local search is introduced to improve the global best particle of each iteration by exploiting the features of ergodicity and randomness. Moreover, a novel technique is proposed to handle bad-defined boundaries; in fact, the possibility to self-enlarge the boundaries of the optimization variables is considered, allowing to achieve the global optimum even if it is located on the boundaries or outside. The algorithm is tested through some benchmark functions and engineering design problems, showing good results, followed by an application regarding the problem of time-suboptimal manoeuvres for satellite formation flying, where the inverse dynamics technique, together with the B-splines, is employed. This analysis proves the ability of the proposed algorithm to optimize control problems related to space engineering, obtaining better results with respect to more common and used algorithms in literature

World Press Photo 2012: the discursive construction of the Arab Spring

O presente artigo pretende analisar a forma como o fenómeno da Primavera Árabe foi retratado nas fotografias vencedoras do concurso World Press Photo em 2012. As fotografias jornalísticas, embora se apresentem como índices do real, condicionam frequentemente a percepção dos indivíduos e influenciam as suas práticas sociais. Também as fotografias vencedoras do World Press Photo, um dos concursos mais prestigiados de fotojornalismo, em 2012 não fogem ao construtivismo discursivo que molda a representação e a percepção dos acontecimentos. A partir da análise crítica do discurso, nomeadamente dos instrumentos teóricos da semiótica barthesiana e da semiótica social de Gunther Kress e Theo van Leeuwen, procurámos interpretar as 38 fotografias vencedoras do World Press Photo 2012, a fim de reflectirmos sobre o modo como contribuíram para a compreensão da Revolta Árabe e como despertaram o nosso interesse e a nossa imaginação para o desenrolar do conflito.ABSTRACT:This article aims to analyze how the Arab Spring phenomenon was represented in the award-winning photographs of the World Press Photo contest in 2012. Although news photographs are usually seen as indexes of the real, they often limit the perception of individuals and influence their social practices. Also the winning photographs in 2012 of the World Press Photo, one of the most prestigious photojournalism contests, do not escape the discursive constructivism that shapes the representation and perception of events. Drawing from critical discourse analysis, namely from the theoretical tools of barthesian semiotics and Gunther Kress’s and Theo van Leeuwen’s social semiotics, we sought to interpret the 38 award-winning photographs of the World Press Photo contest in 2012, in order to reflect on the way they have contributed to our understanding of the Arab Revolt and aroused our interest and imagination to the unfolding of the conflict.info:eu-repo/semantics/publishedVersio

Open Access

Stable SET knockdown in head and neck squamous cell carcinoma promotes cell invasion and the mesenchymal-like phenotype in vitro, as well as necrosis, cisplatin sensitivity and lymph node metastasis in xenograft tumor model

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth

Emerging bone marrow microenvironment‐driven mechanisms of drug resistance in acute myeloid leukemia: Tangle or chance?

Acute myeloid leukemia (AML) has been considered for a long time exclusively driven by critical mutations in hematopoietic stem cells. Recently, the contribution of further players, such as stromal and immune bone marrow (BM) microenvironment components, to AML onset and progression has been pointed out. In particular, mesenchymal stromal cells (MSCs) steadily remodel the leukemic niche, not only favoring leukemic cell growth and development but also tuning their responsiveness to treatments. The list of mechanisms driven by MSCs to promote a leukemia drug-resistant phenotype has progressively expanded. Moreover, the relative proportion and the activation status of immune cells in the BM leukemic microenvironment may vary by influencing their reactivity against leukemic cells. In that, the capacity of the stroma to re‐program immune cells, thus promoting and/or hampering therapeutic efficacy, is emerging as a crucial aspect in AML biology, adding an extra layer of complexity. Current treatments for AML have mainly focused on eradicating leukemia cells, with little consideration for the leukemia‐damaged BM niche. Increasing evidence on the contribution of stromal and immune cells in response to therapy underscores the need to hold the mutual interplay, which takes place in the BM. A careful dissection of these interactions will help provide novel applications for drugs already under experimentation and open a wide array of opportunities for new drug discovery