Retention of progenitor cell phenotype in otospheres from guinea pig and mouse cochlea

Abstract\ud \ud Background\ud Culturing otospheres from dissociated organ of Corti is an appropriate starting point aiming at the development of cell therapy for hair cell loss. Although guinea pigs have been widely used as an excellent experimental model for studying the biology of the inner ear, the mouse cochlea has been more suitable for yielding otospheres in vitro. The aim of this study was to compare conditions and outcomes of otosphere suspension cultures from dissociated organ of Corti of either mouse or guinea pig at postnatal day three (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical cell therapy.\ud \ud \ud Methods\ud Organs of Corti were surgically isolated from P3 guinea pig or mouse cochlea, dissociated and cultivated under non-adherent conditions. Cultures were maintained in serum-free DMEM:F12 medium, supplemented with epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFα). Immunofluorescence assays were conducted for phenotype characterization.\ud \ud \ud Results\ud The TGFα group presented a number of spheres significantly higher than the bFGF group. Although mouse cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin distributed similarly in otosphere cells from both organisms. We present evidence that otospheres retain properties of inner ear progenitor cells such as self-renewal, proliferation, and differentiation into hair cells or supporting cells.\ud \ud \ud Conclusions\ud Dissociated guinea pig cochlea produced otospheres in vitro, expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting evidence for the presence of inner ear progenitor cells in the postnatal guinea pig. However, there is limited viability for these cells in neonatal guinea pig cochlea when compared to the differentiation potential observed for the mouse organ of Corti at the same developmental stage

VIII Congresso Estadual Paulista sobre Formação de Educadores

O tema proposto para discussão durante o VIII Congresso Estadual Paulista sobre a Formação de Educadores – Modos de ser Educador: Artes e Técnicas – Ciências e Políticas envolve a busca de integração entre as diferentes dimensões que compõem a formação do profissional da educação. O trabalho e o sentido da intervenção social desse profissional se constituem em objeto em torno do qual as análises e interpretações vão recolher os fundamentos de debate sobre cultura como totalidade, incluindo: Artes e Técnicas – Ciências e Políticas. A dinâmica que caracteriza a formação de educadores requer a interpretaçãodesses fundamentos para o constante redimensionamento e definição dos objetivos visando aperfeiçoar o papel do profissional educador na sociedade. Por meio de discussões entrediferentes setores ligados à educação é que podem ser avaliados, preservados ou transformados os móveis que norteiam a formação do educador dentro de contextos culturais/sociais específicos, nos diversos campos, artes, técnicas, ciências e políticas. A disponibilidade de um espaço como o VIII Congresso Estadual Paulista sobre a Formação de Educadores para que estudiosos do tema - Educação - se congreguem e debatam a produção de conhecimento sob diversos ângulos, insere e qualifica esse evento como um processo de contribuição para o aprofundamento de estudos na área educacional. Os Congressos Estaduais Paulistas sobre a Formação de Educadores (CEPFE) vêm acontecendo desde 1990 e têm dedicado ênfase especial à formação de profissionais da educação, nos níveis de ensino fundamental, médio e universitário. Tal conformação do Congresso procura extrapolar questões próprias do padrão formal, para a abordagem de formação do profissional da educação embasada na crítica constante, capaz de dinamizar processos e resultados. Essa pretensão ressalta a importância do envolvimento de diferentes áreas do saber numa discussão sobre significados da produção de conhecimento. Daí poderão provir os resultados esperados a partir das atividades programadas para o VIII Congresso dentre os quais está esse caderno de resumos que ora apresentamos.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status