Stream sediments analysis for geochemical mapping of Romagna Apennines (Northern Italy): monitoring and management tool of environmental resources at various scales

Geochemical mapping is a valuable tool for the control of territory that can be used not only in the identification of mineral resources and geological, agricultural and forestry studies but also in the monitoring of natural resources by giving solutions to environmental and economic problems. Stream sediments are widely used in the sampling campaigns carried out by the world's governments and research groups for their characteristics of broad representativeness of rocks and soils, for ease of sampling and for the possibility to conduct very detailed sampling In this context, the environmental role of stream sediments provides a good basis for the implementation of environmental management measures, in fact the composition of river sediments is an important factor in understanding the complex dynamics that develop within catchment basins therefore they represent a critical environmental compartment: they can persistently incorporate pollutants after a process of contamination and release into the biosphere if the environmental conditions change. It is essential to determine whether the concentrations of certain elements, in particular heavy metals, can be the result of natural erosion of rocks containing high concentrations of specific elements or are generated as residues of human activities related to a certain study area. This PhD thesis aims to extract from an extensive database on stream sediments of the Romagna rivers the widest spectrum of informations. The study involved low and high order stream in the mountain and hilly area, but also the sediments of the floodplain area, where intensive agriculture is active. The geochemical signals recorded by the stream sediments will be interpreted in order to reconstruct the natural variability related to bedrock and soil contribution, the effects of the river dynamics, the anomalous sites, and with the calculation of background values be able to evaluate their level of degradation and predict the environmental risk.

In vitro characterisation and expansion of human regulatory T cells for their in vivo application in the induction of tolerance in haematopoietic stem cell and solid organ transplantation

Solid organ transplantation (SOT) is considered the treatment of choice for many end-stage organ diseases. Thus far, short term results are excellent, with patient survival rates greater than 90% one year post-surgery, but there are several problems with the long term acceptance and use of immunosuppressive drugs. Hematopoietic Stem Cells Transplantation (HSCT) concerns the infusion of haematopoietic stem cells to re-establish acquired and congenital disorders of the hematopoietic system. The main side effect is the Graft versus Host Disease (GvHD) where donor T cells can cause pathology involving the damage of host tissues. Patients undergoing acute or chronic GvHD receive immunosuppressive regimen that is responsible for several side effects. The use of immunosuppressive drugs in the setting of SOT and GvHD has markedly reduced the incidence of acute rejection and the tissue damage in GvHD however, the numerous adverse side effects observed boost the development of alternative strategies to improve the long-term outcome. To this effect, the use of CD4+CD25+FOXP3+ regulatory T cells (Treg) as a cellular therapy is an attractive approach for autoimmunity disease, GvHD and limiting immune responses to allograft after transplantation. Treg have a pivotal role in maintaining peripheral immunological tolerance, by preventing autoimmunity and chronic inflammation. Results of my thesis provide the characterization and cell processing of Tregs from healthy controls and patients in waiting list for liver transplantation, followed by the development of an efficient expansion-protocol and the investigation of the impact of the main immunosuppressive drugs on viability, proliferative capacity and function of expanded cells after expansion. The conclusion is that ex vivo expansion is necessary to infuse a high Treg dose and although many other factors in vivo can contribute to the success of Treg therapy, the infusion of Tregs during the administration of the highest dose of immunosuppressants should be carefully considered.

Probiotics for the prevention/treatment of human diseases and ecological study of the intestinal microbiota

The interest in human intestinal microbiota has increased in the last 20 years and significant advances have been achieved with regard to its composition and functions. The gut microbiota contributes to the maintenance of the host health status and, since alterations in the gut microbiota have been involved in the pathogenesis/progression of some diseases, several studies have focused on the manipulation of its composition. Probiotics are a strategy to maintain/restore the correct balance of gut microbial population and to prevent/treat diseases. The aim of this thesis was to explore the possibility of probiotic supplementation for the prevention/treatment of human diseases and the related study of the intestinal microbial environment. After reviewing studies concerning the use of Bifidobacterium breve as probiotic in paediatric diseases, the effectiveness of a probiotic formulation consisting of two strains of B. breve was assessed in paediatric subjects for the prevention or alleviation of gastrointestinal disorders, including coeliac disease and paediatric obesity. As the emerging role of gut microbiota in neurological diseases, the intestinal microbial environment in amyotrophic lateral sclerosis patients compared to healthy controls and the effects of a probiotic administration were examined. Considering the role of viruses in shaping gut microbiota, gut bacteriophages and bacterial community of preterm infants were investigated. The results evidenced differences in gut microbial composition of healthy controls and diseased subjects in coeliac and amyotrophic lateral sclerosis patients. The probiotic approach was effective in restoring the microbial composition in the former, whereas, in the latter, the influence was focused only on some microbial groups. The probiotic intervention was effective in improving the glyco-insulinemic profile in obese children and in preventing gastrointestinal disorders in healthy newborns. The study of the bacterial and phage composition in preterm infants suggested a transkingdom interplay between bacteria and viruses with a reciprocal influence on their composition.