Designing a cloud and HPC based M&S platform to Investigate the IVD diseases mechanisms

The main objective of the PhD proposal consists of the creation of a platform for IVD Models & Simulations (M&S) tools and their integration into automated workflows, within the HORIZON MSCA Disc4All project. Based on the European Open Science Cloud (EOSC) vision, the expected platform will be a Cloud-based one, furnished with a front-end, to guarantee reproducibility, accessibility and easy use for experts and non-experts. The development of an automated and specialized platform can represent the best hybrid technology with perks on both healthcare data management and computational environments exploitation, given the use of Cloud infrastructures on healthcare software and databases. Though rendering automatic not only the database, but prediction and simulation models in a user-friendly integrated system, may facilitate a difficult diagnosis and forward therapy, especially considering the various forces at play in a multi-omics data analysis of its kind

The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells

open12noBreast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.openPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, AngeloPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, Angel

The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines

We investigated the cytotoxic interactions of romidepsin, a histone deacetylase inhibitor, and lenalidomide, an immunomodulatory agent, in a T-cell lymphoma preclinical model. Hut-78 and Karpas-299 cells were treated with romidepsin and lenalidomide alone and in combination. The interaction between romidepsin and lenalidomide was evaluated by the Chou–Talalay method, and cell viability and clonogenicity were also evaluated. Apoptosis, reactive oxygen species (ROS) levels, and cell cycle distribution were determined by flow cytometry. ER stress, caspase activation, and the AKT, MAPK/ERK, and STAT-3 pathways were analyzed by Western blot. Combination treatment with romidepsin and lenalidomide had a synergistic effect in Hut-78 cells and an additive effect in Karpas-299 cells at 24 hours and did not decrease the viability of normal peripheral blood mononuclear cells. This drug combination induced apoptosis, increased ROS production, and activated caspase-8, −9, −3 and PARP. Apoptosis was associated with increased hallmarks of ER stress and activation of UPR sensors and was mediated by dephosphorylation of the AKT, MAPK/ERK, and STAT3 pathways.The combination of romidepsin and lenalidomide shows promise as a possible treatment for T-cell lymphoma. This work provides a basis for further studies

Cytogenetic and molecular characterization of durum wheat chromosome transfers with 1D-associated gluten protein genes and their pyramiding

Gluten quality of bread wheat is known to be mainly associated with high- (HMW-GS) and low-(LMW-GS) molecular weight glutenin subunits encoded by Glu-1 (L arm of group-1 chromosomes) and Glu-3 (S arm of group-1 chromosomes) genes, respectively, with the 1D alleles of such genes having the major impact on bread making properties. Transfer of chromosomal segments containing the Glu-D1 and Gli-D1/Glu-D3 loci was successfully achieved in a number of instances resorting to chromosome engineering. Using this strategy, we isolated two 1A-1D recombinant lines, in which the Gli-D1/Glu-D3 genes and the Glu-D1d allele (HMW-GS "5+10") were separately transferred into the 1AS and 1AL arm, respectively, of recipient durum wheat lines (named PS and PL, respectively). Also, a detailed genetic map of both recombinant chromosome arms was developed. Stable PS + PL double-recombinant lines have been obtained as a result of homologous recombination in the 1A portions shared by the two recombinant chromosomes present in PS x PL hybrids. Preliminary quality tests suggest that the Glu-D3 + Glu-D1d combined presence could determine a slight increase of gluten quality parameters over those associated with Glu-D1d alone

Perceptions of Caring Behavior Among Undergraduate Nursing Students: A Three-Cohort Observational Study

Introduction: Increase in the knowledge of “caring science” among nurses plays a key role in ensuring a correct caring behavior towards patients. Caring training for students is a priority in nursing education, but unfortunately there are limited and conflicting studies which explore this outcome. The purpose of this observational study was to explore the perceptions of caring behaviors by nursing students during their clinical practice training in order to highlight if the level of caring behaviors changes as the nursing course progresses. Materials and Methods: The Caring Behaviors Inventory-24 (CBI-24) was administered to 331 students, enrolled in the three years of an Italian Nursing Course, who accepted to participate in the study (89.2% response rate). The data were analyzed using SPSS software version 26.0 (SPSS Inc., Chicago, IL). Results: The total mean score of CBI-24 was 4.82 in the first, 5.12 in the second and 5.26 in the third-year students. The CBI-24 dimensions “Responding to individual needs” and “Being with” obtained the highest scores among the students of the first year. At the end of the first year, our students were already able to perform expressive caring, whereas instrumental caring developed at a high level in the second and third years. We did not highlight any statistically significant difference between the two gender CBI-24 item scores. Conclusion: In light of our results, we put in evidence that Nursing Degree Programme favours the development in students of both relational and technical components of caring behaviors. We hope that in future students’ self-assessment of caring behaviors could be considered an educational outcome for Nursing Programme

Fine Tuning of the Mechanical Properties of Bio-Based PHB/Nanofibrillated Cellulose Biocomposites to Prevent Implant Failure Due to the Bone/Implant Stress Shielding Effect

A significant mechanical properties mismatch between natural bone and the material forming the orthopedic implant device can lead to its failure due to the inhomogeneous loads distribution, resulting in less dense and more fragile bone tissue (known as the stress shielding effect). The addition of nanofibrillated cellulose (NFC) to biocompatible and bioresorbable poly(3-hydroxybutyrate) (PHB) is proposed in order to tailor the PHB mechanical properties to different bone types. Specifically, the proposed approach offers an effective strategy to develop a supporting material, suitable for bone tissue regeneration, where stiffness, mechanical strength, hardness, and impact resistance can be tuned. The desired homogeneous blend formation and fine-tuning of PHB mechanical properties have been achieved thanks to the specific design and synthesis of a PHB/PEG diblock copolymer that is able to compatibilize the two compounds. Moreover, the typical high hydrophobicity of PHB is significantly reduced when NFC is added in presence of the developed diblock copolymer, thus creating a potential cue for supporting bone tissue growth. Hence, the presented outcomes contribute to the medical community development by translating the research results into clinical practice for designing bio-based materials for prosthetic devices

Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial

Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle

From winery waste to bioactive compounds and new polymeric biocomposites: a contribution to the circular economy concept

The paper aims at optimising and validating possible routes toward the full valorisation of grape agrowaste to produce bioactive molecules and new materials. Starting from Merlot red pomace, phenol complex mixtures were successfully extracted by using two different approaches. Extracts obtained by solvent-based (SE) technique contained up to 46.9 gGAeq/kgDW of total phenols. Depending on the used solvent, the prevalence of compounds belonging to different phenol families was achieved. Pressurized liquid extraction (PLE) gave higher total phenol yields (up to 79 gGAeq/kgDW) but a lower range of extracted compounds. All liquid extracts exerted strong antioxidant properties. Moreover, both SE and PLE extraction solid residues were directly exploited (between 5 and 20% w/w) to prepare biocomposite materials by direct mixing via an eco-friendly approach with PHBV polymer. The final composites showed mechanical characteristics similar to PHVB matrix. The use of pomace residues in biocomposites could therefore bring both to the reduction of the cost of the final material, as a lower amount of costly PHBV is used. The present research demonstrated the full valorisation of grape pomace, an agrowaste produced every year in large amounts and having a significant environmental impact

Evaluation of an interprofessional education intervention in partnership with patient educators

Background and aim of the work: Patient involvement in interprofessional education is a novel approach to building collaborative and empathic skills in students. However, this area of teaching is lacking in rigorous studies. The project aimed to evaluate whether an interprofessional education intervention in partnership with patient educators (IPE-PE) would increase readiness for interprofessional learning and empathy in health sciences students. Methods: This is the report of a didactic innovation project. Participants included 310 undergraduate health sciences students who took part in an IPE-PE intervention. Data were collected before and after the training, using the Readiness for Interprofessional Learning Scale (RIPLS) and the Jefferson Scale of Empathy-Health Professions Student version ( JSE-HPS). Only at the end of the intervention, a data collection form was administered to explore the value of the patient educator in the training and to investigate the socio-demographic variables. Results: The mean age of participants was 21±3.2 SD years and 76% were female. The Wilcoxon signed-rank test showed significant changes from before to after the IPE-PE in the RIPLS total score (m=42.7±5.8 SD vs 44.62±5.9 SD, z=-4.168, P<0.001) and in the JSE-HPS total score (m=112.7±12.5 SD vs 116.03±12.8 SD, z=-4.052, P<0.001). Conclusions: Our students reported that IPE-PE had helped them to become more effective healthcare team members, to think positively about other professionals, and to gain an empathic understanding of the perspective of the person being cared for. The results of the project confirm that the intervention promoted the development of empathy, fostering a better understanding of the patient-centred perspective