Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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Exploring intersectionality issues in entrepreneurial finance: Policy responses and future research directions

Main Message Entrepreneurial finance scholars (and policy-makers) need to adopt an intersectional approach to their analysis (and policy-making) and pay more attention to the interplay between the owner-manager characteristics of ethnicity/race, gender, and social class. Shorter Title of the manuscript Exploring intersectionality issues in entrepreneurial finance Key points Since most literature on entrepreneurial finance treats ethnicity/race, gender, and class separately, an intersectional approach to analysis is complex, whether social (race, gender, social class) or situational characteristics (entrepreneur versus migrant/social or health care worker). Women, ethnic minorities, and working-class people are disadvantaged when seeking finance. We integrate the literature and proposes intersectionality as a framework for policy-makers, since the interplay between these characteristics can be addressed to develop innovative methods of finance

Human milk oligosaccharides: Functionality in infants Oligosacaridos de la leche materna: Evidencia de su funcionalidad en lactantes

Human milk is a very complex fluid that contains numerous bioactive compounds. Among them, it includes very high con-centrations of oligosaccharides (human milk oligosaccharides [HMOs]) that group more than a hundred complex sugars. We present an extensive review of the composition and functions of the HMOs, highlighting the influence of the maternal genotype FUT2 on the type and concentration, being the latter much higher in FUT secretory women. The HMOs are non digestible in the intestine of the infant, therefore, they provide a substrate for the development of an intestinal microbiota, mainly rich in bifidobacteria. In addition, since some of these HMOs share some structural sequences with receptors for intestinal pathogens, they act as decoy blocking these receptors prevent-ing their adhesion and proliferation. The benefits of the con-sumption of these HMOs are considered unique, therefore the synthesis of HMOs structurally identical to those found in breast milk and with similar functionality demonstrated through clinical studies, opens a very interesting line of re-search in the field of infant nutrition. The first clinical studies conducted with HMOs are analyzed, considering necessary new clinical intervention trials in infants to confirm these ef-fects on the immune system and reducing the frequency of re-spiratory and gastrointestinal infections

Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype

The thrombin receptor protease activated receptor-1 (PAR-1) is overexpressed in metastatic melanoma cell lines and tumor specimens. Previously, we demonstrated a significant reduction in tumor growth and experimental lung metastasis after PAR-1 silencing via systemic delivery of siRNA encapsulated into nanoliposomes. Gene expression profiling identified a 40-fold increase in expression of Maspin in PAR-1–silenced metastatic melanoma cell lines. Maspin promoter activity was significantly increased after PAR-1 silencing, suggesting that PAR1 negatively regulates Maspin at the transcriptional level. ChIP analyses revealed that PAR-1 decreases binding of Ets-1 and c-Jun transcription factors to the Maspin promoter, both known to activate Maspin transcription. PAR-1 silencing did not affect Ets-1 or c-Jun expression; rather it resulted in increased expression of the chromatin remodeling complex CBP/p300, as well as decreased activity of the CBP/p300 inhibitor p38, resulting in increased binding of Ets-1 and c-Jun to the Maspin promoter and higher Maspin expression. Functionally, Maspin expression reduced the invasive capability of melanoma cells after PAR-1 silencing, which was abrogated after rescuing with PAR-1. Furthermore, tumor growth and experimental lung metastasis was significantly decreased after expressing Maspin in a metastatic melanoma cell line. Moreover, silencing Maspin in PAR-1–silenced cells reverted the inhibition of tumor growth and experimental lung metastasis. Herein, we demonstrate a mechanism by which PAR-1 negatively regulates the expression of the Maspin tumor-suppressor gene in the acquisition of the metastatic melanoma phenotype, thus attributing an alternative function to PAR-1 other than coagulation