Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells

Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment

Oral Immunotherapy for Food-Allergic Children: A Pro-Con Debate.

The prevalence of food allergy has increased in recent years, especially in children. Allergen avoidance, and drugs in case of an allergic reaction, remains the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanut, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization through the consumption of an increasing amount of a food allergen, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current pediatric OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, pediatric OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.post-print6382 K

Diabetic ketoacidosis at the onset of disease during a national awareness campaign: a 2-year observational study in children aged 0-18 years

After a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013-2014 in Italy, we aimed to verify a possible decline in the incidence of DKA at onset during a national prevention campaign

Call to action: Air pollution, asthma, and allergy in the exposome era

International audienc

VALIDAZIONE PRELIMINARE DI UN QUESTIONARIO SUL CARICO EXTRALAVORATIVO NELL’INTERFACCIA CASA-LAVORO IN OTTICA DI GENERE

Scopo del presente studio è quello di validare uno strumento anamnestico parametrico a supporto del Medico Competente nel rilevare difficoltà individuali del lavoratore legate al genere, con particolare attenzione agli aspetti di conciliazione che potrebbero avere ricadute su problemi di salute e sicurezza in ambito lavorativ

Cognition in COVID-19 infected patients undergoing invasive ventilation: results from a multicenter retrospective study.

A growing number of scientific contributions suggest that COVID-19 infection can lead to impairment of cognition, mainly in executive functions and memory domains, even in the absence of frank neurological pathologies. The primary objective of this retrospective study is to evaluate the frequency and type of inefficiencies in a selection of cognitive tests administered to a sample of subjects who, following infection, required invasive assisted ventilation and were admitted to rehabilitation wards for the treatment of functional impairment. Fifty-seven subjects were enrolled. The recruited patients undergone an assessment of verbal and visuospatial memory and executive functions, upon entry into the rehabilitation department, after discharge from intensive care. The following tests were administered: Rey Auditory Verbal Learning Test (AVLT) (immediate and delayed recall), Rey-Osterrieth Complex Figure Test (ROCFT) (copy and delayed recall), Stroop Color-Word Test, and Trail Making Test (TMT, A and B). Deficient scores, in beyond 25% of subjects, were found in the copy of the ROCFT (32.1% of subjects), and in the delayed recall of ROCFT (27.2%). Between 10 and 20% of patients presented an abnormal result in delayed recall of AVLT (16.07%), and Stroop Test (time, 15.6%, error, 11.5%). Less than 10% of the sample had abnormal performances on TMT (A, 3.5%, and B, 9.4%), and in AVLT immediate recall (8.9%). Correlations of the performances with age, sex, and education were also found. This paper highlights the high incidence of abnormal cognitive performances in this specific subpopulation of patients with COVID-19 infection