Human milk glycosaminoglycans: the state of the art and future perspectives

Recently, a complete characterization and detailed evaluation of the glycosaminoglicans of human milk were performed. The total glycosaminoglican content in milk from healthy mothers having delivered term or preterm newborns showed a constant pattern which was essentially composed of two main polysaccharides: chondroitin sulfate (60-70%) and heparin (30-40%). Moreover, considerable variations of glycosaminoglican concentration were found during the first month of lactation, the highest values being present in colostrum compared to mature milk. Metabolism and potential biological functions of human milk glycosaminoglicans are hypothesized and future studies are encouraged

Technology Evolution and Tax Compliance: Evidence from Rwanda

Narrowing the ‘information problem’ through technology. Data on economic transactions is crucial for tax administrations to be able to enforce tax compliance. One way of obtaining more information is through technology. In the last decade, African tax administrations have increasingly adopted technological advances such as integrated systems, electronic filings, and electronic billing machines (EBMs). EBMs allow taxpayers to digitise their transactions and transfer billing information automatically to the revenue authority. They also hold high potential for taxpayers, as they can allow firms to lower administrative and compliance costs, streamline transactions, improve their record-keeping, strengthen their capacity, and in the case of small businesses, attract clients and engage in trade thanks to the improved accuracy. Rwanda is one of the fastest growing and most technology-oriented countries in Africa, whose tax authority, despite a steadily rising tax-to-GDP ratio, still faces challenges such as limited resources and high levels of informality. In 2013, the Rwandan Revenue Authority (RRA) introduced EBMs through a machine called EBM1. The machine used a SIM card, through which VAT registered taxpayers transmitted sale transaction data to the RRA in real-time. Like any technology, it came with several issues, such as high costs, storage limitations and lack of support. As a result, an improved free software version called EBM2 was rolled out in 2017, which could digitize and store receipts and capture core business information like inventory and item types. Summary of African Tax Administration Paper 30

Switch from enzyme replacement therapy to oral chaperone migalastat for treating fabry disease: real-life data

The treatment options for Fabry disease (FD) are enzyme replacement therapy (ERT) with agalsidase alfa or beta, and the oral pharmacological chaperone migalastat. Since few data are available on the effects of switching from ERT to migalastat, we performed a single-center observational study on seven male Fabry patients (18-66 years) to assess the effects of the switch on renal, cardiac, and neurologic function, health status, pain, lyso-Gb3, α-Gal A activity and adverse effects. Data were retrospectively collected at time of diagnosis of FD (baseline, T0), and after 12 months of ERT (T1), and prospectively after 1 year of therapy with migalastat (T2). No patient died or reported renal, cardiac, or cerebrovascular events during the study period. The predefined measures for cardiac, renal and neurologic function, and FD-related symptoms and questionnaires were stable between baseline and the switch, and remained unchanged with migalastat. However, a significant improvement was observed in left ventricular mass index from baseline to T2 (p = 0.016), with a significative difference between the treatments (p = 0.028), and in median proteinuria from T2 vs T1 (p = 0.048). Moreover, scores of the BPI improved from baseline to T1, and remained stable with migalastat. Plasma lyso-Gb3 levels significantly decreased from baseline to T1 (P = 0.007) and T2 (P = 0.003), while did not significantly differ between the two treatments. α-Gal A activity increased from T0 to T2 (p < 0.0001). The frequency of adverse effects under migalastat and ERT was comparable (28% for both drugs). In conclusion, switching from ERT to migalastat is valid, safe and well tolerated

The isoprenoid end product N6-Isopentenyladenosine inhibits inflammation in bronchial epithelial cells through modulating the NFκB pathway

N6-Isopentenyladenosine (iPA) is a cytokinin identified in plants but also present in a free form or as a modified nucleoside bound to selenocysteine tRNA in human cells. It is an adenosine modified by an isopentenyl chain which derives from dimethylallil pyrophosphate (DMAPP), an intermediate of the mevalonate pathway. iPA is required for efficient translational decoding of selenoproteins, and can modulate a variety of biological processes including cell cycle progression, DNA synthesis and apoptosis (1). Recently, it has been shown that iPA can exhibit immunomodulatory and anti-inflammatory properties by activating NK cells and modulating cytokine production in a way depending on the concentration used (2). In order to further investigate the anti-inflammatory properties of iPA and its possible mechanisms of action, we analyzed its ability to inhibit TNFα-induced inflammation, either in normal human bronchial epithelial cells or in a model of exacerbated inflammation represented by bronchial cells derived from a Cystic Fibrosis (CF) patient bearing the ΔF508 mutation. Results showed that iPA inhibited IL-8 and RANTES release in both type of cells in a different manner. The analysis of the key enzymes of the STAT3 and NF-κB signalling pathways showed that iPA decreased the phosphorylation of STAT3 enzyme and markedly increased the expression of the direct NF-κB inhibitor, IκBα. These results were corroborated analyzing directly the NF-κB activity in HEK 293/T cells transfected with a NF-κB reporter plasmid. In these cells, iPA was also able to decrease IκBα levels. Of interest, we found that iPA also increased the expression of the antioxidant selenoprotein glutathione peroxidase only in CF cells. Altogether these data suggest that iPA can negatively regulate inflammation with a general mechanism of action involving the inhibition of NF-κB pathway but also propose that, in the presence of an altered inflammatory response such as in CF disease, iPA might act by modulating expression and/or synthesis of glutathione peroxidase

Low-grade myofibroblastic sarcoma of the breast.

n/

Diencephalic Syndrome Due to Optic Pathway Gliomas in Pediatric Patients: An Italian Multicenter Study

: Diencephalic syndrome (DS) is a rare pediatric condition associated with optic pathway gliomas (OPGs). Since they are slow-growing tumors, their diagnosis might be delayed, with consequences on long-term outcomes. We present a multicenter case series of nine children with DS associated with OPG, with the aim of providing relevant details about mortality and long-term sequelae. We retrospectively identified nine children (6 M) with DS (median age 14 months, range 3-26 months). Four patients had NF1-related OPGs. Children with NF1 were significantly older than sporadic cases (median (range) age in months: 21.2 (14-26) versus 10 (3-17); p = 0.015). Seven tumors were histologically confirmed as low-grade astrocytomas. All patients received upfront chemotherapy and nutritional support. Although no patient died, all of them experienced tumor progression within 5.67 years since diagnosis and were treated with several lines of chemotherapy and/or surgery. Long-term sequelae included visual, pituitary and neurological dysfunction. Despite an excellent overall survival, PFS rates are poor in OPGs with DS. These patients invariably present visual, neurological or endocrine sequelae. Therefore, functional outcomes and quality-of-life measures should be considered in prospective trials involving patients with OPGs, aiming to identify "high-risk" patients and to better individualize treatment