Role of neuronal and inducible nitric oxide synthases in the guinea pig ileum myenteric plexus during in vitro ischemia and reperfusion

Background Intestinal ischemia and reperfusion (I/R) injury leads to abnormalities in motility, namely delay of transit, caused by damage to myenteric neurons. Alterations of the nitrergic transmission may occur in these conditions. This study investigated whether an in vitro I/R injury may affect nitric oxide (NO) production from the myenteric plexus of the guinea pig ileum and which NO synthase (NOS) isoform is involved. Methods The distribution of the neuronal (n) and inducible (i) NOS was determined by immunohistochemistry during 60 min of glucose/oxygen deprivation (in vitro ischemia) followed by 60 min of reperfusion. The protein and mRNA levels of nNOS and iNOS were investigated by Westernimmunoblotting and real time RT-PCR, respectively. NO levels were quantified as nitrite/nitrate. Key Results After in vitro I/R the proportion of nNOSexpressing neurons and protein levels remained unchanged. nNOS mRNA levels increased 60 min after inducing ischemia and in the following 5 min of reperfusion. iNOS-immunoreactive neurons, protein and mRNA levels were up-regulated during the whole I/R period. A significant increase of nitrite/nitrate levels was observed in the first 5 min after inducing I/R and was significantly reduced by Nx-propyl-L-arginine and 1400 W, selective inhibitors of nNOS and iNOS, respectively. Conclusions & Inferences Our data demonstrate that both iNOS and nNOS represent sources for NO overproduction in ileal myenteric plexus during I/R, although iNOS undergoes more consistent changes suggesting a more relevant role for this isoform in the alterations occurring in myenteric neurons following I/R

NF1 regulates mesenchymal gliblastoma plasticity and aggressiveness through the AP-1 transcription factor FOSL1

The molecular basis underlying glioblastoma (GBM) heterogeneity and plasticity is not fully understood. Using transcriptomic data of human patient-derived brain tumor stem cell lines (BTSCs), classified based on GBM-intrinsic signatures, we identify the AP-1 transcription factor FOSL1 as a key regulator of the mesenchymal (MES) subtype. We provide a mechanistic basis to the role of the neurofibromatosis type 1 gene (NF1), a negative regulator of the RAS/MAPK pathway, in GBM mesenchymal transformation through the modulation of FOSL1 expression. Depletion of FOSL1 in NF1-mutant human BTSCs and Kras-mutant mouse neural stem cells results in loss of the mesenchymal gene signature and reduction in stem cell properties and in vivo tumorigenic potential. Our data demonstrate that FOSL1 controls GBM plasticity and aggressiveness in response to NF1 alterations

Implementing a school-based comprehensive sexual health education intervention in Italy: experiences from the field

Introduction: This study describes the preliminary results of a School-based sexuality education (SBSE) pilot activity developed and implemented within EduForIST project, funded by the Italian Ministry of Health. Methods: The pilot activity (5 modules of 2 hours each delivered per classroom) targeted lower secondary schools students. A total of 20 schools located in 4 different Italian regions participated. The educators were staff of several HIV/AIDS civil society organisations operating in Italy. A 2-days intensive workshop for educators was performed. Pre and post tests were conducted. Results: At the time of submission, pre-test results were available from 14 classrooms of 5 schools within 2 Italian Regions, for a total of 266 students. Among these, 37,4% were unsure that personal identity is built through social comparison; 21,8% reported that emotions don't get more intense during adolescence, while 18,1% were unsure about the response; 42,1% reported a higher level of uncertainty concerning the definitions of gender identity, sexual orientation and stereotype. The highest level of uncertainty were reported for STIs symptoms (58,7%), impact of treatment on HIV+ people (61,9%) and efficacy of contraceptive pills in preventing STIs (43,4%). The post-test results were available for 153 students. Pre/post analysis showed an increase of correct answers (p < 0.05) for 12 of 15 items investigated. A total of 102 students responded to the satisfaction questionnaire, with preliminary positive results. Conclusions: Since activities are ongoing, further data will be soon available for more exhaustive analyses. Early pre/post evaluations suggested that the pilot experience was effective in enhancing knowledge and decreasing uncertainty in the different domains addressed in the pilot. Evidence collected through this study shall raise awareness among decision makers on the urgency of introducing CSE in Italian school curricula and inform future policy options

Embracing ambiguity in management control and decision-making processes:On how to design data visualizations to prompt wise judgement

Making decisions when managing organizations always involves the constant management of ambiguity and a great deal of complexity due to uncertainties and the intrinsic political nature of every decision-making processes. This paper argues that in order for management accounting to deal effectively with this ambiguity and uncertainty, both must be embraced, not suppressed, by the design of data visualizations produced by management controls as aids to the decision-making processes. Drawing on studies in rhetoric, alongside others on the rhetorical and communicative power of images and visualizations, this paper identifies a series of principles that can contribute to the development of a visual rhetorical framework to inform the design of data visualization (e.g. dashboards, business reports). The need to conceive of data visualisations beyond their representational function, and the principles that are identified, are then illustrated through the visual rhetorical analysis of a complex dashboard utilised in the programme management of the construction of a large airport terminal. The paper ends with an outline of a research agenda for the future design of data visualization in accounting, and beyond