Nkx2-5+Islet1+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Participate in Restoring Stromal Network Integrity

SummarySecondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5+Islet1+ lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

Eduarda Mansilla: la Biografía, Redes familiares y amicales. Los Epistolarios. Los escritos dispersos. Hacia un estudio crítico integral

El estudio de la vida y obra de Eduarda Mansilla se enmarca en la crítica sobre literatura argentina decimonónica escrita por mujeres, así como en la historia de la vida privada y su interconexión con el mapa político-social de la época, especialmente visible en las grandes familias de la clase dirigente. El corpus específicamente literario de Mansilla aún no había sido efectivamente cerrado y determinado. Se sabía, sobre todo por las memorias de su hijo Daniel García-Mansilla (1950), de la existencia de obras varias, y de escritos de crítica de arte que no han podido ubicarse. Nos constaba además, por compulsas ya realizadas, que diversos textos de la autora subsisten dispersos en publicaciones periódicas de la época, nacionales y en el extranjero. Tanto ese material, como cuanto se pudiera conseguir en lo que hace a epistolarios, crónicas, memorias, diarios y escritos testimoniales de todo tipo guardados en archivos públicos y privados, era precario y se hallaba expuesto a la desaparición y al deterioro. Hasta el presente los asedios a la vida/obra de nuestra autora se han mantenido dentro de marcos más o menos acotados, subordinados a un objetivo mayor: una edición textual, la presentación de un panorama femenino (“argentinas”, “mujer romántica”), la historia de la composición musical en la Argentina, en el que esta figura singular se engarza, pero no constituyeron investigaciones de envergadura autónoma. Lo antedicho confirmó la necesidad de localizar y rescatar la producción total de la autora a través de la compulsa de archivos públicos y privados, lo que nos permitió establecer una biografía confiable de Eduarda Mansilla que, aspiramos, se constituya en obra de consulta. Los resultados de esta investigación se publicaron en la Colección EALA de la editorial Corregidor.Our study of Eduarda Mansilla´s life and works is carried on within the field of criticism about Argentine Nineteenth-Century literature written by women, as well as in the history of private lifeand its interconnection with the political and social map of that period, which was especially visiblein certain traditional families. The specifically literary corpus of Mansilla has not yet been closednor clearly determined. Thanks to the memories written by one of her sons, Daniel García-Mansilla(1950), it is known that Mansilla has produced several literary pieces that disappeared and are notavailable to us nowadays. In addition, there are many other diverse literary works that have beenoriginally published nationally and abroad in a series of periodicals, newspapers and literary journalsthat are still inaccessible to the researchers. These materials, along with memoires, travel journals,personal notes, and any other disperse writing production by Eduarda are scattered, hidden inlibraries, unpublished and in danger of material destruction. Until today, research about Mansillahas been framed within certain fields such as the study of romanticism, Women writings, musicalcomposition, always with the goal of pursuing a critical edition. But none of them constitutes initself an independent research project. The above-mentioned confirmed the necessity of localizingand rescuing the total production of this writer nowadays scattered in public as well as in privatearchives, with the goal of achieving a serious and reliable biography of Eduarda Mansilla which,we expect, will become a referent in our discipline. The results of this research were published inthe EALA Collection Corregidor publisher

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015