Characterization of epidermal growth factor-like domain 7 (EGFL7) expression in normal endometrium and in the endometrium of women with poor reproductive outcomes.

STUDY QUESTION: Could epidermal growth factor-like domain 7 (EGFL7) be a factor involved in the preparation of the endometrium for implantation and could its dysregulation be implicated in poor reproductive outcomes? SUMMARY ANSWER: EGFL7 is highly expressed in the endothelium and glandular epithelium throughout the menstrual cycle; it is upregulated by stromal cells in secretory phase and appears strongly reduced in endometrial biopsies and isolated stromal cells of women with unexplained recurrent pregnancy loss (uRPL) and recurrent implantation failure (RIF). WHAT IS KNOWN ALREADY: The secreted factor EGFL7, originally identified as a gene primarily expressed in endothelial cells, is also expressed by the mouse blastocyst and by mouse and human trophoblast cells. It regulates trophoblast migration and invasion by activating NOTCH1 signaling. NOTCH1 has been demonstrated to play a fundamental role in endometrial receptivity and its dysregulation may be involved in selected pregnancy complications characterized by altered endometrial receptivity, such as uRPL. STUDY DESIGN, SIZE, DURATION: This is an exploratory study for which 84 endometrial biopsies were collected from normally fertile women, as well as from women with uRPL and RIF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Samples were collected from women in both the proliferative and secretory phases of the menstrual cycle and stratified into three sub-groups according to the patient clinical history: 20 fertile women (8 in proliferative and 12 in secretory phase), 41 women with uRPL (6 in proliferative and 35 in secretory phase), and 27 women with RIF (8 in proliferative and 19 in secretory phase). Immunohistochemistry, real-time PCR, and western blot analyses were performed to study the expression of EGFL7 and NOTCH1, as well as the NOTCH target genes. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis of spatial and temporal distribution of EGFL7 in endometrial biopsies from fertile women revealed higher levels of EGFL7 in samples from the secretory phase compared to proliferative phase. The expected expression of EGFL7 in endothelial cells was shown as well as the novel, not previously reported, expression in endometrial glands and stromal cells. EGFL7 was significantly reduced in the endometrium of women with uRPL and RIF in the secretory phases and this was associated with a downregulation of the NOTCH1 signaling pathway. Human recombinant EGFL7 was able to activate the NOTCH1 signaling pathway in endometrial stromal cells (EndSCs) obtained from fertile women but not in cells from uRPL or RIF patients. EndSCs from fertile women and decidualized in vitro for three days showed an upregulation of EGFL7 expression, whereas cells obtained from women with uRPL and RIF and decidualized in vitro did not. LIMITATIONS, REASONS FOR CAUTION: This study was conducted with a relatively small number of patient samples. Although results are highly reproducible and consistent, additional observations from multicentric cohorts would strengthen the relevance of the data. Moreover, this is an in vitro study, which might only partially represent the in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS: Our results demonstrate for the first time that EGFL7 is new player involved in decidualization and provide new insights into the pathophysiology of selected implantation defects and early pregnancy complications. Our studies have revealed that alterations in EGFL7 expression and the consequent dysregulation of NOTCH signaling are potential underlying causes of RIF and uRPL. Our results might have therapeutic relevance, as the EGFL7/NOTCH pathway may represent a potential target for medical intervention. STUDY FUNDING/COMPETING INTEREST(S): This study has been supported by the Grant for Fertility Innovation 2017 (Merck KGaA). There are no competing interests to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Responding to a school SARS-CoV-2 outbreak: Insights and policy implications emerging from the pandemic.

Background: The SARS-CoV-2 pandemic has affected also the school environment. Prolonged closures and the weakness of available data prevent a definitive answer to the question of school transmission. We report our experience of responding to COVID-19 cases in the school setting, presenting a case study of the management of an outbreak in a large school. Methods: The LHA/ASL Roma 1 has organized the School Units with a structure firmly rooted in the territory. At the local level, the District Unit mainly manages the relationship with schools, while the Hygiene and Public Health Service of the Prevention Department holds a coordinating and facilitating role. The HPHS carries out contact tracing activities facilitated by the schools, through the figure of the COVID-19 Contact Person, who is specifically trained to manage the preliminary stages of the reports. Results: Following several reports of COVID-19 suspect cases from two schools and, after a complex phase of contact tracing, it was possible to identify the major transmission chains. Furthermore, we performed a population-based screening on the entire school. Beyond the known transmission chains, for which quarantine was already in place, only five additional cases emerged, all asymptomatic, out of 1,231 swabs tested with RT-PCR. Conclusions: Our experience confirms that an active interaction between the school and the School Unit made it possible to quickly control a potentially dangerous outbreak. The large-scale screening test demonstrated the substantial absence of collateral transmission chains. Effective contact tracing allowed to set forth a successful response. Our model of intervention can be used to support public health protocols regarding school outbreaks.

Social inequalities in the metropolitan area of Rome. A multidisciplinary analysis of the urban segregation of the "formerly-Bastogi" compound.

BACKGROUND: This study tries to evaluate, through a multidisciplinary approach, the relationship between urban structure, isolation and distribution of social determinants of health, in the so-called "formerly-Bastogi, a compound, with more than 1,500 inhabitants, located in north-western Rome, Italy. METHODS: The architectural-urban analysis, conducted through site visits and evaluations of urban situation, showed how strongly the compound is isolated from the neighbourhoods, and structurally degraded. The socio-demographic analysis, based on the National Census data, showed significant differences in the distribution of the social determinants of health between "formerly-Bastogi" and the surrounding areas. RESULTS: The area under study appears to be isolated from the surrounding urban space, both because of social and architectural factors. This situation could have some association with inhabitants' health. CONCLUSIONS: If our preliminary investigation was useful for a diagnosis of the situation, a more complete - qualitative and quantitative - investigation of the context will be needed to plan appropriate multidisciplinary health-promoting interventions.