β-Galactosylceramidase Deficiency Causes Bone Marrow Vascular Defects in an Animal Model of Krabbe Disease

Abstract: Krabbe disease (KD) is an autosomal recessive sphingolipidosis caused by the deficiency of the lysosomal hydrolase β-galactosylceramidase (GALC). Oligodendroglia degeneration and demyelination of the nervous system lead to neurological dysfunctions which are usually lethal by two years of age. At present, the only clinical treatment with any proven efficacy is hematopoietic stem-cell transplantation, which is more effective when administered in the neonatal period to presymptomatic recipients. Bone marrow (BM) sinusoidal endothelial cells (SECs) play a pivotal role in stem cell engraftment and reconstitution of hematopoiesis. Previous observations had shown significant alterations of microvascular endothelial cells in the brain of KD patients and in Galc mutant twitcher mice, an authentic model of the disease. In the present study, we investigated the vascular component of the BM in the femurs of symptomatic homozygous twitcher mice at postnatal day P36. Histological, immunohistochemical, and two-photon microscopy imaging analyses revealed the presence of significant alterations of the diaphyseal BM vasculature, characterized by enlarged, discontinuous, and hemorrhagic SECs that express the endothelial marker vascular endothelial growth factor receptor-2 (VEGFR2) but lack platelet/endothelial cell adhesion molecule-1 (CD31) expression. In addition, computer-aided image analysis indicates that twitcher CD31−/VEGFR2+ SECs show a significant increase in lumen size and in the number and size of endothelial gaps compared to BM SECs of wild type littermates. These results suggest that morphofunctional defects in the BM vascular niche may contribute to the limited therapeutic efficacy of hematopoietic stem-cell transplantation in KD patients at symptomatic stages of the disease

La nostra ricerca per la salute di tutti, 1934-2004

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Evaluating the Effectiveness of Internet-Based Communication for Public Health: Systematic Review

Background: Communicating strategically is a key issue for health organizations. Over the past decade, health care communication via social media and websites has generated a great deal of studies examining different realities of communication strategies. However, when it comes to systematic reviews, there is fragmentary evidence on this type of communication. Objective: The aim of this systematic review was to summarize the evidence on web institutional health communication for public health authorities to evaluate possible aim-specific key points based on these existing studies. Methods: Guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, we conducted a comprehensive review across 2 electronic databases (PubMed and Web of Science) from January 1, 2011, to October 7, 2021, searching for studies investigating institutional health communication. In total, 2 independent researchers (AN and SS) reviewed the articles for inclusion, and the assessment of methodological quality was based on the Kmet appraisal checklist. Results: A total of 78 articles were selected. Most studies (35/78, 45%) targeted health promotion and disease prevention, followed by crisis communication (24/78, 31%), general health (13/78, 17%), and misinformation correction and health promotion (6/78, 8%). Engagement and message framing were the most analyzed aspects. Few studies (14/78, 18%) focused on campaign effectiveness. Only 23% (18/78) of the studies had an experimental design. The Kmet evaluation was used to distinguish studies presenting a solid structure from lacking studies. In particular, considering the 0.75-point threshold, 36% (28/78) of the studies were excluded. Studies above this threshold were used to identify a series of aim-specific and medium-specific suggestions as the communication strategies used differed greatly. Conclusions: Overall, the findings suggest that no single strategy works best in the case of web-based health care communication. The extreme variability of outcomes and the lack of a unitary measure for assessing the end points of a specific campaign or study lead us to reconsider the tools we use to evaluate the efficacy of web-based health communication