Short bowel syndrome in età pediatrica: dall'eziopatogenesi al trattamento

Short Bowel Syndrome (SBS) in children is a condition of intestinal malabsorption and dysmotility, caused by rare congenital malformations or acquired diseases, requiring extensive bowel surgical resection which in severe cases can lead to irreversible intestinal failure. Nowadays, the management of pediatric patients affected by SBS is multidisciplinary, involving different possible strategies of treatment: total parenteral nutrition, surgical intestinal lengthening up to intestinal transplantation. The main aim of all these approaches is to promote bowel absorption, but none of them is free from complications that may impair children quality of life. Based on these considerations, this Research Project aims to identify new options to manage and treat SBS. Hence, two aspects were considered: a clinical and an experimental one. As known, the management of SBS patients requires a careful follow-up by a multispecialistic team, able to survey their possible short- and long-term complications and their progressive weaning from parenteral support. Considered this, the clinical part of this Research Project focused on the evaluation of citrulline as a reliable serum marker of residual bowel function. The goal was to verify the possibility of suggesting it for routine dosage in case of intestinal failure, similarly to creatinine in renal impairment and for transaminases in hepatic failure. Briefly, we identified a sample population consisting of 10 SBS patients, age ≤ 5 years and residual bowel length (after surgery) ≤ 100 cm. Patients followed-up with parenteral and enteral nutrition programs and were subjected to citrulline dosages at least 6 weeks after surgery. At the end of the clinical evaluation, we highlighted that serum values of citrulline are strongly related with both the residual intestinal length and the duration of their dependence on parenteral support (p < 0.01). Likewise, the experimental research turned its attention to Tissue Engineering that is a new medical science which aims to achieve functionally active tissue substitutes by scaffolds, cells and growth factors. The second part of the Research Project focused on the possibility to develop a bio-synthetic scaffold for tissue engineering applications in SBS. We manufactured, according to a protocol we patented, new hydrogels based on polyvinyl alcohol with a degree of oxidation of 1% and 2% respectively. The purpose of the chemical oxidation was to confer to the derived biomaterial a certain biodegradation rate. Hence, oxidized hydrogels obtained via physical cross-linking (freezing-thawing) were compared to native PVA hydrogels for their morpho-mechanical and biological properties by means of ultrastructural analysis with scanning electron microscopy, tensile tests, swelling index analysis, and in vivo biodegradation studies. These investigations showed that the strength and the stiffness of the polymer are significantly related to the chemical modification as they decrease along with the oxidation degree; conversely, the swelling and the biodegradation rate increase along with it. The obtained results led us to identify in scaffolds prepared by using 1% Oxidized PVA the supports with the most adequate morpho-mechanical and biodegradation properties to our purposes. Hereafter, it was set up a composite scaffold in 1% Oxidized PVA cross-linked with decellularized intestinal extracellular matrix (ECM). The combination of the polymer with the bioactive matrix allowed us to obtain a support with good mechanical properties and able to promote cell growth and proliferation. Briefly, the small intestine of adult rats was removed and decellularized according to the detergent-enzymatic protocol by Meezan. After having assessed the effectiveness of the procedure (DAPI staining) the acellular matrix was characterized by histological staining (hemotoxylin/eosin). Thereafter, the extracellular matrix (intact and homogenized) was crosslinked with 1% Oxidized PVA and the ability of the composite scaffold to support cell adhesion and proliferation was investigated using a primary culture of adipose mesenchymal stem cells. After 7 days from seeding, a significant cell growth on the composite scaffolds was observed in comparison with the nude polymeric support. Finally, based on of the TESI (Small Intestine Tissue Engineering) model, the scaffold was implanted in the omentum of adult rats; after 4-weeks, composite scaffolds demonstrated their ability to induce the formation of a composite pseudoepithelial tissue with intestinal-like features

Gibbard-Satterthwaite Games

The Gibbard-Satterthwaite theorem implies the ubiquity of manipulators-voters who could change the election outcome in their favor by unilaterally modifying their vote. In this paper, we ask what happens if a given profile admits several such voters. We model strategic interactions among Gibbard-Satterthwaite manipulators as a normal-form game. We classify the 2-by-2 games that can arise in this setting for two simple voting rules, namely Plurality and Borda, and study the complexity of determining whether a given manipulative vote weakly dominates truth-telling, as well as existence of Nash equilibria

Virtual Tours to Promote the Remote Customer Experience

Today, virtual reality and augmented reality can allow people to interact with products and places in a very realistic way. In this direction, the use of immersive virtual tours (VTs) can improve the users' experience, their perceptions, attitudes and even intended behaviours as potential or actual consumers. The paper focuses on a traditional Italian cheese product and defines a transdisciplinary, multimodal approach where VT helps the remote customer experience based on a VT application to virtually visit a Parmigiano Reggiano cheese dairy, using cutting- edge virtual reality set-up. The paper describes how to create a virtual tour of industrial plants by mapping the main actions, from the storytelling definition, to the plant digitization, until the creation of the virtual, immersive and multimodal application using Unity3D. The VT combines visual experience with gesture recognition and audio stimulation, adding also olfactory cues, in order to create an interactive and realistic experience

Urokinase thrombolysis as a rescue treatment for midgut volvulus ischemia

Abstract Midgut volvulus in infants may lead to extreme short bowel syndrome. Strategies to avoid post-ischemia bowel loss have been proposed, involving thrombolysis prior to a definitive surgical treatment. Haemorrhagic risks in these patients may withhold from this approach. Herein we describe the use of urokinase systemic infusion after an unsatisfactory second look laparotomy, performed in a term baby with midgut volvulus. Continuous infusion of urokinase was given for seventeen hours prior to a third laparotomy. A total of 25 cm of small bowel were finally kept in place. Twelve months after the 1st laparotomy the patient was on oral feeding 125 calories/Kg/day. This case showed the possible rescue role of a fibrinolytic agent against persistent ischemia after the second look laparotomy for neonatal volvulus

Tissue-engineered grafts from human decellularized extracellular matrices: A systematic review and future perspectives

Tissue engineering and regenerative medicine involve many different artificial and biologic materials, frequently integrated in composite scaffolds, which can be repopulated with various cell types. One of the most promising scaffolds is decellularized allogeneic extracellular matrix (ECM) then recellularized by autologous or stem cells, in order to develop fully personalized clinical approaches. Decellularization protocols have to efficiently remove immunogenic cellular materials, maintaining the nonimmunogenic ECM, which is endowed with specific inductive/differentiating actions due to its architecture and bioactive factors. In the present paper, we review the available literature about the development of grafts from decellularized human tissues/organs. Human tissues may be obtained not only from surgery but also from cadavers, suggesting possible development of Human Tissue BioBanks from body donation programs. Many human tissues/organs have been decellularized for tissue engineering purposes, such as cartilage, bone, skeletal muscle, tendons, adipose tissue, heart, vessels, lung, dental pulp, intestine, liver, pancreas, kidney, gonads, uterus, childbirth products, cornea, and peripheral nerves. In vitro recellularizations have been reported with various cell types and procedures (seeding, injection, and perfusion). Conversely, studies about in vivo behaviour are poorly represented. Actually, the future challenge will be the development of human grafts to be implanted fully restored in all their structural/functional aspects

Correction: Recent advances in the synthesis of analogues of phytohormones strigolactones with ring-closing metathesis as a key step

Correction for 'Recent advances in the synthesis of analogues of phytohormones strigolactones with ring-closing metathesis as a key step' by Chiara Lombardi, et al., Org. Biomol. Chem., 2017, DOI: 10.1039/c7ob01917c

Pivotal role of micro-CT technology in setting up an optimized lung fibrosis mouse model for drug screening

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with no curative pharmacological treatment. The most used animal model of IPF for anti-fibrotic drug screening is bleomycin (BLM)-induced lung fibrosis. However, several issues have been reported: the balance among disease resolution, an appropriate time window for therapeutic intervention and animal welfare remain critical aspects yet to be fully elucidated. In this study, C57Bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA) following either double or triple administration. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 4 weeks after BLM administration. Quantitative micro-CT measurements highlighted that triple BLM administration was the ideal dose regimen to provoke sustained lung fibrosis up to 28 days. These results were corroborated with lung histology and Bronchoalveolar Lavage Fluid cells. We have developed a mouse model with prolonged lung fibrosis enabling three weeks of a curative therapeutic window for the screening of putative anti-fibrotic drugs. Moreover, we have demonstrated the pivotal role of longitudinal micro-CT imaging in reducing the number of animals required per experiment in which each animal can be its own control. This approach permits a valuable decrease in costs and time to develop disease animal models