O processo de interação entre os sujeitos na constituição da aquisição da linguagem escrita

Orientador: Maria Laura Trindade Mayrink-SabinsonDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Estudos da LinguagemResumo: A presente pesquisa focaliza a aquisição da linguagem escrita, em sua fase inicial. O corpus da mesma constitui-se em um estudo longitudinal ocorrido num periodo de doze meses. Com a coleta dos dados objetivou-se analisar situações interativas de constituição da escrita inicial. Assim discuto, aqi a importância do papel do outro no processo de aquisição da linguagem escrita a partir da análise das trocas reei procss, estabelecidas nas situações de interação ocorridas entre três sujeitos investigadora e gêmeas idênticas (J. - outro que já domina a base alfabética da escrita e G.- outro que ainda não alcançara a base alfabética da escrita, na época da coleta dos dados. Para realizar a análise dos dados tomo como ponto de partida uma perspectiva calcada na interação como constitutiva do conhecimento.-Procuro olhar os dados a partir de uma concepção de linguagem que a vê como resultante do movimento das atividades linguísticas realizadas entre os sujeitos, via interação. Por outro lado, não desprezo a perspectiva na qual se defende a singularidade do sujeito em sua relação com a linguagem. A abordagem teórica deste trabalho leva em conta tanto o social quanto a singularidade dos sujeitos. Deste modo, o trabalho mostrou como relevantes os sequintes pontos: a) Que as interlocuções "outras" ocorridas no processo interativo produzem o movimento dos sujeitos levando-os a se constituírem como tais : b) Que cada sujeito estabelece o que considera relevante, nestas interações: é a marca da singularidade. c) Que o processo interativo é movido pelas diferenças, pelas singularidadesAbstract: Not informed.MestradoMestre em Linguístic

miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors

B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.This study was supported by grants from the Ministry of Science and Innovation (SAF2012-34327, PLE2009-0147, and PSE-010000-2009-3), the Comunidad Autonoma de Madrid (S2010/BMD-2420), the Instituto de Salud Carlos III (RETICS.TERCEL), and the European Commission (Proposal 242038) to AB, (BFU2012-35258 and RYC-2009-04341) to JAB, and fellowship FPU-AP2010-5951 to FMC. We thank JL Toran and S Mendez-Ferrer for critical discussions of the manuscript; RM Carmona for help with the animal procedure; Fatima Sanchez Cabo for statistic and bioinformatic assistance, and K. McCreath for editorial support

Mania as Debut of Cushing's Syndrome

This is a case of a patient affected by Cushing syndrome that was admitted at the hospital due to hormonal problems. He had presented psychiatric symptoms that were mistakenly considered not directly connected to the pathology causing the clinical condition, but a mere psychological reaction to it

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

CoRISpe (Cohorte Nacional de VIH pediátrica de la RED RIS).[Background] Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution.[Methods] Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit.[Results] 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5–6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).Peer reviewe

Atenuación del artefacto metálico post cirugía de columna lumbar mediante protocolo de obtención de imagen en tomografía computarizada multicorte. Estudio de cohortes.

Fundamento. Las imágenes obtenidas mediante estudios con TC pueden ser alteradas por la presencia de artefactos metálicos, induciendo en ocasiones a malinterpretación en la correcta ubicación de los tornillos pediculares en columna lumbar. El objetivo de este trabajo es desarrollar un protocolo de atenuación del artefacto metálico con el propósito de reducir el artefacto generado por los tornillos pediculares de titanio en aquellos pacientes a los que se ha requerido instrumentación lumbar, permitiendo a los cirujanos de columna realizar un diagnóstico preciso de la ubicación del tornillo pedicular instrumentado. Material y métodos. En la primera parte del trabajo se realizó un estudio observacional, analítico, longitudinal y retrospectivo en 23 pacientes (103 tornillos pediculares) a los que se requirió artrodesis lumbar por patología degenerativa. En el postoperatorio se les realizó un estudio con TC secuencial evaluando la sobredimensión generada por el artefacto del tornillo, aplicando un protocolo estándar de obtención de imágenes. En la segunda parte del estudio se diseñó un estudio observacional, analítico, longitudinal y prospectivo empleando un equipo de TCMC de 64 coronas aplicando un protocolo específico de adquisición de imagen sobre 18 pacientes (104 tornillos pediculares) intervenidos mediante artrodesis lumbar. Resultados. En la primera parte del estudio el artefacto medio a ambos lados del tornillo que se genera tras el estudio de TC es de 1,045 mm (DE: 0,45). En el grupo en el que se aplica el protocolo de atenuación del artefacto tras la TCMC la sobredimensión fue de 0,005 en la porción proximal del tornillo y de 0,025 en la parte distal del tornillo. Conclusiones. Los resultados obtenidos sugieren que tras la aplicación del protocolo de atenuación del artefacto en equipo de TCMC de 64 coronas el artefacto es reducido a unas dimensiones similares a la dimensión real del tornillo pedicular.Background. In postoperative patients with metallic implants, CT scans can become less effective due to metal-related artifacts. The purpose of our study was to evaluate the effectiveness of a specific metal artifact reduction image protocol, in order to reduce the metal artifact caused by titanium pedicular screws in patients undergoing lumbar pathology by lumbar fusion. This enables surgeons to make an accurate diagnosis of the exact placement of inserted pedicle screws, making this the preferred image modality for assessing screw position after surgery. Methods. In the first part of the study, CT scans were performed on 23 patients (103 titanium alloy pedicle screws) undergoing a lumbar instrumented fusion for treatment for degenerative disease with a standard image acquisition protocol evaluating the possible overdimension caused by the artifact. In the second part, a prospective study was performed using 64-slice multidetector-row computed tomography (MDCT) on 18 patients (104 titanium alloy pedicle screws) undergoing a lumbar instrumented fusion using a specific image acquisition protocol. Results. Our results show that in the sequential CT scan group, mean overdimension (on each side) due to brightness was 1.045 mm (SD 0.45). In the 64-slice multichannel CT group, mean overdimension (on each side) due to brightness was 0.005 mm at the proximal part of the screw and 0.025 mm at the distal part of the screw. Conclusions. The use of a specific metal artifact reduction image protocol in MDCT produces a minimal artifact following lumbar fusion with pedicle screws

Production of spinach in intensive Mediterranean horticultural systems can be sustained by organic-based fertilizers without yield penalties and withlow environmental impacts

Agricultural production of leafy vegetables in Mediterranean countries aims to achieve high yields without elevated nitrate contents in the edible parts. This implies an adjusted nutrient management, especially of nitrogen (N), in irrigated horticultural systems under semiarid conditions. These horticultural systems are highly relevant in SE Spain from an economic perspective. However, the management of N fertilizer, generally applied in large amounts (150–250 kg N ha−1 in a split application), could trigger losses of reactive N to the environment. The use of novel fertilizers may fulfill the nitrogen requirements of the crop, but should also help to decrease the environmental impacts of production, thus achieving carbon-neutral horticultural systems through (e.g.) enhancement of carbon (C) stocks and greenhouse gases (GHG) emission abatement. In this experiment, eight different fertilizing scenarios at a normalized N application rate of 150 kg N ha−1 were assessed in terms of crop yields, nutrients uptake, C stocking capacity, and yield-scaled GHG emissions. Inorganic NPK fertilizers, digestates, biosolids, composts, and vermicomposts were included among this set of fertilizers. Our results show that organic-based stabilized materials, especially composts, lowered the NO3 − concentration in spinach leaves, in comparison to organic raw materials and synthetic fertilizers. They also produced yields similar to those of slow-release synthetic fertilizers, but with a significant increase in soil organic C 61 days after application. In general, N2O emissions were positively affected by the treatments. Nevertheless, direct N2O emissions were generally low (the highest emission factor, 0.13, being for the biosolid treatment) due to the combined mitigating effect of both the edapho-climatic conditions and the management practices. In general, cumulative CO2 emissions were high in all organic scenarios compared to the control treatment (299 kg C-CO2 ha−1), the highest values being observed in the treatment with biosolid (589 kg C-CO2 ha−1), probably due to differences in the labile organic C contents. In conclusion, some of the organic-based treatments showed multiple positive effects: on crop quality (i.e. leaf N content), crop yields, and GHG mitigation potential. Based on our results, the use of these materials represents an optimized N fertilizer strategy to help achieve a circular economy, by closing nutrient loops and decreasing the environmental impacts of horticultural production systems in semiarid regions of southern Europ

InforMing the PAthway of COPD Treatment (IMPACT Trial) Single-Inhaler Triple Therapy (Fluticasone Furoate/Umeclidinium/Vilanterol) Versus Fluticasone Furoate/Vilanterol and Umeclidinium/Vilanterol in Patients With COPD: Analysis o the Western Europe and North America Regions

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airflow limitation and progressive respiratory symptoms.1 Global public health trends estimate that the COPD burden will continue to rise, with COPD deaths estimated to increase to 4.4% of all deaths in Europe and 6.3% in the World Health Organization-defined region of the Americas by 2060.2 There are differences in the COPD burden in different regions reflecting variations in etiology,3,4 disease severity,5 symptoms,6 medication use,7 and health care systems and utilization.7 These differences may help inform therapeutic strategies to optimize therapeutic approaches to reducing symptoms and exacerbation risk.1 In the global InforMing the PAthway of COPD Treatment (IMPACT) trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates and improved lung function and health-related quality of life versus FF/VI or UMEC/VI dual therapy in patients ≥40 years of age with symptomatic COPD and a history of exacerbations.8 Within trial populations, regional differences such as patient characteristics, treatment patterns, access to care and cultural/socioeconomic factors may dictate treatment choices and influence disease severity and progression in particular geographical locations. For example, a meta-analysis conducted in 2015 comprising 123 studies between 1990 and 2010 found that the overall prevalence of COPD as well as the rate of increase was higher in the Americas (including both North and South America) compared with Europe.9 Furthermore, a cross-sectional study assessing the burden of COPD symptoms in the United States and Europe found variations between patients across countries who had experienced at least 1 symptom of COPD.10 In Europe, patients with more frequent symptoms were more likely to experience worsening of symptoms and unexpected hospitalization. Whereas in the United States, patients with more frequent symptoms were not only more likely to experience worsening of symptoms but also longer lasting symptoms and a longer length of exacerbations.10 A further difference was that treatment adherence was higher in the United States than Europe, however, adherence was consistent across patients in Europe when assessed by modified Global initiative for chronic Obstructive Lung Disease (GOLD) 2014 groups11 but varied in the United States with adherence highest in the GOLD Group C and lowest in Group A.10 Therefore, it is important to evaluate how overall population results pertain to patients treated in particular regions. As IMPACT is one of the largest trials conducted in patients with COPD to date, we have the unique opportunity to analyze study outcomes in patients enrolled in Western Europe and North America, the 2 main regions from an enrollment perspective

Reference-grade genome and large linear plasmid of Streptomyces rimosus: pushing the limits of Nanopore sequencing

[EN] Streptomyces rimosus ATCC 10970 is the parental strain of industrial strains used for the commercial production of the important antibiotic oxytetracycline. As an actinobacterium with a large linear chromosome containing numerous long repeat regions, high GC content, and a single giant linear plasmid (GLP), these genomes are challenging to assemble. Here, we apply a hybrid sequencing approach relying on the combination of short- and long-read next-generation sequencing platforms and whole-genome restriction analysis by using pulsed-field gel electrophoresis (PFGE) to produce a high-quality reference genome for this biotechnologically important bacterium. By using PFGE to separate and isolate plasmid DNA from chromosomal DNA, we successfully sequenced the GLP using Nanopore data alone. Using this approach, we compared the sequence of GLP in the parent strain ATCC 10970 with those found in two semi-industrial progenitor strains, R6-500 and M4018. Sequencing of the GLP of these three S. rimosus strains shed light on several rearrangements accompanied by transposase genes, suggesting that transposases play an important role in plasmid and genome plasticity in S. rimosus. The polished annotation of secondary metabolite biosynthetic pathways compared to metabolite analysis in the ATCC 10970 strain also refined our knowledge of the secondary metabolite arsenal of these strains. The proposed methodology is highly applicable to a variety of sequencing projects, as evidenced by the reliable assemblies obtainedSIThis work was supported as part of the European project “Thoroughly Optimised Production Chassis for Advanced Pharmaceutical Ingredients” (grant ID 720793, European Union’s Horizon 2020 Research and Innovation Program) and by the Slovenian Research Agency (P4-0116, P4-0077, and P1-0034). L.S. is supported by a Slovenian Research Agency young researcher grant (35220200570), and M.T. is supported by grant C3330-19-952047 funded by Republic of Slovenia Ministry of Education, Science, and Sport and the European Union European Regional Development Fun

The qualification of an enrichment biomarker for clinical trials targeting early stages of Parkinson’s disease

As therapeutic trials target early stages of Parkinson’s disease (PD), appropriate patient selection based purely on clinical criteria poses significant challenges. Members of the Critical Path for Parkinson’s Consortium formally submitted documentation to the European Medicines Agency (EMA) supporting the use of Dopamine Transporter (DAT) neuroimaging in early PD. Regulatory documents included a comprehensive literature review, a proposed analysis plan of both observational and clinical trial data, and an assessment of biomarker reproducibility and reliability. The research plan included longitudinal analysis of the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) and the Parkinson’s Progression Markers Initiative (PPMI) study to estimate the degree of enrichment achieved and impact on future trials in subjects with early motor PD. The presence of reduced striatal DAT binding based on visual reads of single photon emission tomography (SPECT) scans in early motor PD subjects was an independent predictor of faster decline in UPDRS Parts II and III as compared to subjects with scans without evidence of dopaminergic deficit (SWEDD) over 24 months. The EMA issued in 2018 a full Qualification Opinion for the use of DAT as an enrichment biomarker in PD trials targeting subjects with early motor symptoms. Exclusion of SWEDD subjects in future clinical trials targeting early motor PD subjects aims to enrich clinical trial populations with idiopathic PD patients, improve statistical power, and exclude subjects who are unlikely to progress clinically from being exposed to novel test therapeutics