Interleukin-17A promotes parietal cell atrophy by inducing apoptosis

Background & Aims: Atrophic gastritis caused by chronic inflammation in the gastric mucosa leads to the loss of gastric glandular cells, including acid-secreting parietal cells. Parietal cell atrophy in a setting of chronic inflammation induces spasmolytic polypeptide expressing metaplasia, a critical step in gastric carcinogenesis. However, the mechanisms by which inflammation causes parietal cell atrophy and spasmolytic polypeptide expressing metaplasia are not well defined. We investigated the role of interleukin-17A (IL-17A) in causing parietal cell atrophy. Methods: A mouse model of autoimmune atrophic gastritis was used to examine IL-17A production during early and late stages of disease. Organoids derived from corpus glands were used to determine the direct effects of IL-17A on gastric epithelial cells. Immunofluorescent staining was used to examine IL-17A receptors and the direct effect of signaling on parietal cells. Mice were infected with an IL-17A-producing adenovirus to determine the effects of IL-17A on parietal cells in vivo. Finally, IL-17A neutralizing antibodies were administered to mice with active atrophic gastritis to evaluate the effects on parietal cell atrophy and metaplasia. Results: Increased IL-17A correlated with disease severity in mice with chronic atrophic gastritis. IL-17A caused caspase-dependent gastric organoid degeneration, which could not be rescued with a necroptosis inhibitor. Parietal cells expressed IL-17A receptors and IL-17A treatment induced apoptosis in parietal cells. Overexpressing IL-17A in vivo induced caspase-3 activation and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining in parietal cells. Finally, IL-17A neutralizing antibody decreased parietal cell atrophy and metaplasia in mice with chronic atrophic gastritis. Conclusions: These data identify IL-17A as a cytokine that promotes parietal cell apoptosis during atrophic gastritis, a precursor lesion for gastric cancer. Keywords: IL-17A, Atrophy, Metaplasia, Apoptosi

Data Analytics in Health 4.0: Extracting Knowledge from Big Data in Pandemic Times

Knowledge Extraction from Big Data in Digital Health domain during covid-19 pandem

Determinación volumétrica de calcio y magnesio, con la sal disódica del ácido etilendiaminotetracético : Su aplicación a materiales silícicos, en especial refractarios

Los trabajos realizados sobre la determinación de dureza en aguas, utilizandocomo reactivos la sal disódica del ácido etilendiaminotetracético,y el empleo de Eriochrome Black T como indicador del puntofinal de la valoración conjunta de Ca y Mg, y murexide para la valoraciónseparada del Ca , han servido como punto de partida para laaplicación de este mismo método en la determinación de Ca y Mg en materialesrefractarios. El empleo de microbureta y ligeras modificaciones en la técnica permitieronobtener errores más pequeños que los habituales para estasconcentraciones de Ca y Mg, que son muy inferiores a las que se encuentranen aguas. La exactitud obtenida en soluciones puras es deun mg/l (expresado como carbonato de calcio) para el valor del Ca yde 2 mg/l para el valor calculado del Mg. Para obtener el valor del Ca y del Mg separadamente se ensayó eliminarel Ca como oxalato y titular Mg remanente en el filtrado enpresencia de Eriochrome Black T. Los errores obtenidos son mucho mayoresdebido a la incompleta separación del Ca. Esto unido a la mayorcomplejitud de la técnica, hace que sea preferido el método quevalora Ca utilizando murexide como indicador. El límite de aplicabilidad para la determinación conjunta de Ca y Mg y la de Ca separadamente es de 0,06 mg en 50 ml de muestra (1,2 mg/lexpresado como carbonato de Ca.). Hemos estudiadoy ensayado el efecto de distintas concentraciones dediversos iones de existencia común y posible en materiales refractarios,estableciendo para cada casos el valor máximo que puede alcanzarse. Se ha llegado a establecer que para poder aplicar el métodosin inconvenientes, la solución en que se realizan las titulaciones,no debe contener más de: 2 mg/l de Cu, 10 mg/l de Fe+++, 15 mg/l de Al, 6 mg/l de Mn++, y 100 mg/l de Si03(2-). Al aplicar el método a muestras de refractarios, se debieron solucionar algunos inconvenientes provocados por la presencia de clorurode amonio existente en la solución por provenir de procesos anteriores y que da al pH valor inadecuado, que no permite la correcta actuación de los indicadores. El método propuesto tiene una precisión de 0,1 g de OCa/100 g dematerial y 0,14 g de OMg/lOO g de material refractario. Aplicadoel método a una serie de muestras, los resultados obtenidos se compararoncon los proporcionados por métodos comunmente utilizados . Las recuperaciones realizadas sobre muestras de refractarios permitenasegurar que es posible obtener valores de una gran precisión. Esto unido a su rapidez y simplicidad hace que el método propuestopueda ser considerado superior a todos los utilizados para la determinación de Ca y Mg en materiales refractarios en análisis de rutina.Fil: Alderuccio, Víctor. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Curriculum innovations and the ‘politics of legitimacy’ in teachers’ discourse and practice in a Mozambican primary school

In 2004, Mozambique introduced a new competency-based curriculum framed around the principles of culturally responsive pedagogy. Teachers need to strategically use local languages, traditions and culture to build on what children bring from home and share with their families to bridge the gap between schools and communities. This study is a qualitative ethnography of the teaching and learning process in one suburban primary school in Mozambique. The aims of the study were to explore teachers’ ideas, values, and understanding about the teaching and learning process, and to reflect on how these views, which are manifested in their classroom practices, influenced the implementation of curriculum changes at the classroom level. The study conceptualised the new educational policy in Mozambique as a discourse that has introduced in the field of teachers’ practices new pedagogic possibilities and frame of references. Informal conversations, interviews, and observations of lessons and school dynamics were the main methods used for the process of data collection. Teachers, students, parents and community members participated in the study. Ethnography as methodology offered the possibility to gain multi-layered insights into those contextual, social, and cultural realities around which teachers create meanings for their roles and actions, attribute significance to them, and build relations with students, parents, and community members. Understanding how these realities were represented and reproduced in teachers’ discourse and practice was regarded as a precondition to interrogating teachers’ interpretations of changes. The study combined a Bourdieusian sociological analysis of the teaching and learning process with a postcolonial critique. Whereas Bourdieu’s tools of field, habitus and capital supported an understanding of the ‘whys’ behind what is going on at classroom level and the cultural and ideological assumptions underpinning teachers’ practices, a postcolonial critique exposed the rules of classification and exclusion underpinning the ‘hows’ of teachers’ pedagogies. The findings of the study showed that the pedagogic discourse of the new curriculum does not resonate with teachers’ understanding of their roles, practices and professional identities. The conception of ‘schooling as an extractive process’ and the construction of Portuguese as the most important symbolic cultural capital legitimised the process of alienation between schooling and home socialisation and sustained the power relations, determining the separation between inschool and out-of-school languages and knowledges. If, on the one side, teachers dismissed their responsibility to transform and integrate local knowledges into the official curriculum by constructing themselves as implementers of an educational policy that they did not fully grasp, then on the other side, in the process of making sense of the new curriculum, the socio-cultural values that teachers attached to it were challenging their field positions and maintenance. Teachers maintained their distinction through their ‘Portugueseness’. The ‘Portuguese-only discourse’ was the most dominant ‘doxa’, taken-forgranted by teachers in their practices, despite the fact that Portuguese as Language of Learning and Teaching was perceived as one of the main challenges for student learning. The implication of the study relates to the cultural micro-politics of teachers’ identities. To attend to the introduction of curriculum changes as a technical matter fails to address the power-relations embedded in the teaching and learning process. The new pedagogic possibilities fostered by the curriculum are not succeeding. Without the re-narrativisation of how teachers think about them in order to build new field positions and meanings that resonate with changes, the reform seems unlikely to succeed

Culture and heritage for a just transition to climate-neutral and smart cities. Text mining supporting New European Bauhaus elements detection

Cities are at the forefront in linking their socio-economic development to culture and heritage that they are slowly acknowledging as a way to also address climate change. Cultural participation can influence a diverse range of social impact areas, such as health and wellbeing, social cohesion and intercultural dialogue, innovation, and education, as well as community-driven urban and territorial renewal and development. The sense of heritage ownership is a complex relationship between individual, collective, and institutional claims that can leverage action and better governance. With the New European Bauhaus (NEB) initiative launched in 2021, the European Union pledges culture's contribution to the European Green Deal and advocates the role of cultural institutions, as they play a vital role in strengthening community engagement. This article illustrates to what extent culture (arts, heritage, cultural, and creative industries) and NEB principles are mainstreamed into recent and innovative urban energy and climate policies to drive behavioral change and improve networking and multi-stakeholder commitment. We have focused on a sample of the 100 EU Mission Cities. By analyzing their road maps for climate-neutrality and smartness, the Climate City Contracts (CCCs), we have addressed the following questions: – Do cities rely on culture and heritage for a just transition? – What is the role of arts, heritage, cultural, and creative Industries in their pathways for a just transition? – Do these actions take advantage of digitalization? Based on the vocabulary categorization, we have started developing a text mining method that may support extending the analysis of “culture for climate action”—related elements to a broader number and types of urban transition policies. We have interpreted the CCCs sample providing a high-quality human-annotated corpus. The aim is to train a future artificial intelligence model that could help assess impacts and identify other culture and heritage-based experiences to enhance “Knowledge for Policy” toward the NEB application in cities

An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered

Not all central nervous system lymphomas are created equal

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Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: the future for therapy of autoimmune disease?

Based on the principle that immune ablation followed by HSC-mediated recovery purges disease-causing leukocytes to interrupt autoimmune disease progression, hematopoietic stem cell transplantation (HSCT) has been increasingly used as a treatment for severe autoimmune diseases. Despite clinically-relevant outcomes, HSCT is associated with serious iatrogenic risks and is suitable only for the most serious and intractable diseases. A further limitation of autologous HSCT is that relapse rates can be high, suggesting disease-causing leukocytes are incompletely purged or the environmental and genetic determinants that drive disease remain active. Incorporation of antigen-specific tolerance approaches that synergise with autologous HSCT could reduce or prevent relapse. Further, by reducing the requirement for highly toxic immune-ablation and instead relying on antigen-specific tolerance, the clinical utility of HSCT could be significantly diversified. Substantial progress has been made exploring HSCT-mediated induction of antigen-specific tolerance in animal models but studies have focussed on primarily on prevention of autoimmune diseases. However, as diagnosis of autoimmune disease is often not made until autoimmune disease is well developed and populations of autoantigen-specific pathogenic effector and memory T cells have become well established, immunotherapies must be developed to address effector and memory T-cell responses which have traditionally been considered the key impediment to immunotherapy. Here, focusing on T-cell mediated autoimmune diseases we review progress made in antigen-specific immunotherapy using HSCT-mediated approaches, induction of tolerance in effector and memory T cells and the challenges for progression and clinical application of antigen-specific ‘tolerogenic’ HSCT therapy

A Preliminary Analysis of a Nuzi Scribal Family in view of an application in the ENEA-GRID

Assyriology uses new technologies for computer encoding of cuneiform texts, to support the analysis and management of a great deal of data coming from tablets. At the present, integrating e-tools in the GRID virtual environment opens new perspectives in the analysis of ancient texts and enables ENEA-GRID for e-Humanities, with a particular attention devoted to Assyriology. Therefore, after a preliminary study, an experimental application of new technologies to the Nuzi Corpus has been carried out, using Multilingual Text Mining in ancient languages, in view of an integration into the digital environment of the ENEA GRID. This innovative approach into the study of cuneiform corpora may influence software developments and collaborative working in order to match the specific needs of scholars communities

Transformation of marginal zone lymphoma to Hodgkin lymphoma

Marginal zone lymphomas (MZLs) make up 5% to 10% of non-Hodgkin lymphomas. In the United States, extranodal MZL (EMZL) is the most common subtype (61%), followed by nodal MZL (NMZL; 30%) and splenic MZL (SMZL; 9%), with an increased incidence across all subtypes with age. MZL is characterized by an indolent course with a characteristic clinical presentation by subtype. EMZL frequently presents with localized mucosa involvement at diagnosis. SMZL commonly involves the spleen, bone marrow, and peripheral blood and less frequently the lymph nodes. NMZL typically presents with lymphadenopathy, occasionally involving the bone marrow or peripheral blood, and without splenic or extranodal involvement. The overall survival (OS) of patients with MZL is favorable with a 5-year relative survival rate of 90%