Vascular endothelial growth factor-A and Poly(A) binding protein-interacting protein 2 expression in human head and neck carcinomas: correlation and prognostic significance

Vascular endothelial growth factor-A (VEGF-A) has been demonstrated to play an important role in tumour angiogenesis and to influence prognosis in many cancers. However its prognostic value in head and neck squamous cell carcinomas (HNSCCs) remains controversial. Therefore, we investigated the clinical relevance of VEGF-A expression in HNSCCs and analysed whether its expression was associated with PAIP2 protein levels, a VEGF-A mRNA-binding partner that strongly regulates VEGF-A expression in tissue culture. We determined the correlation of VEGF-A and PAIP2 protein levels, quantitatively evaluated in tumour tissue homogenates from 54 patients with HNSCC, to clinicopathological parameters. We showed that VEGF-A expression in HNSCC is correlated to the stage of tumour differentiation (P=0.050) and is an independent prognostic factor for progression-free survival (P=0.001) and overall survival (P=0.0004). In a pharynx carcinoma cell line, we demonstrated by RNA interference that VEGF-A expression is closely controlled by PAIP2. Moreover, in human HNSCCs, VEGF-A expression is significantly correlated to PAIP2 protein levels (P=0.0018). Nevertheless, PAIP2 expression is associated with neither clinicopathological factors nor patient's survival. Our data suggest that, in contrast to PAIP2 protein levels, which are unrelated to tumour prognosis, VEGF-A expression could serve as a prognostic marker in head and neck cancer and may be helpful for targeted therapies

Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay ( BFU- E and CFU- GM) in short- term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL- 6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients ( 68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU- E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL- 6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/ or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting

Granular flow simulations and experiments for the food industry

Granular media are omnipresent in the food industry, whether as raw materials, intermediate or final products. While a lot has been done already in modelling food processes dealing with liquids, solid and gases, very little exists until now in granular flow modelling. The present thesis takes up the challenge of producing realistic granular simulations via DEM and validating them experimentally. Indeed DEM is one of the most promising granular media simulation approaches, but its wide application is still restrained by the limited number of particles that can be considered and the small collection of comparisons with experimental data. Yet it will be shown in this thesis that DEM is indeed a powerful tool for realistic modelling. We focus on two granular systems relevant to the food industry, for which we carry out in parallel simulations and physical experiments. First we study the size segregation of cereals in a vertically vibrated cereal box. Three configurations are tested experimentally, and compared with simulations achieving a qualitative validation. The importance of convection rolls and the role of particle and wall friction coefficients is illustrated. We extend the study to the ordering behaviour of elongated grains under vertical vibrations. We show that this phenomenon is intrinsic to elongated grains and takes place also in the absence of help from sidewalls. We study the role of particle geometry and vibration acceleration and we provide a novel interpretation in terms of available kinetic energy and relevant potential energy barriers. Building on these results, we study and interpret the shape segregation of rods from spheres. Experiments and simulations fit together nicely. The second food application concerns the flow and dosing from vending machine canisters. Our three dimensional DEM simulation unveils a rich microcosm of particle interactions and provides in particular an unexpected explanation for the decreasing dose mass over time. To make this simulation possible we developed an algorithm to detect the collisions between spherical grains and the helix auger. A dosing experiment using glass beads is successfully compared with a simulation in terms of the evolution of both the surface shape and the dosed mass. Good agreement is reached. Further dosing experiments are performed using a cohesive beverage powder. The effect of the dosing screw design on the flow in the canister is quantified and a dosing coil improving the powder withdrawal across the canister is designed and successfully tested. The quantitative comparisons between experiments and simulations achieved in this work and the insight gained from such simulations show clearly the benefit for the food industry stemming from a coupled use of DEM simulations and experiments

Multidisciplinary model for hospital-territory integrated management of patient with bone fragility: primary and secondary prevention of fractures according to severity and complexity.

The aim of this study was to promote the construction of a real network and a shared diagnostic and therapeutic management model between hospitals and out-of-hospital healthcare services to capture as many patients with bone fragility as possible. Starting from the analysis of the clinical competences present in the province of Pavia, the bone specialists (BSs) organized some educational events involving both general practitioners (GPs) and hospital specialists. The Fracture Liaison Service (FLS) model, the revision of Note 79, the national plan for chronicity and the health reform of the Lombardy Regional Authority supported the structure of our model, in which the roles of clinicians are well defined and based on the complexity and severity of patients. In our method the GP has a central role as clinical manager, facilitating patient management and communication between the specialists and the BS. In January 2019, the Therapeutic Care Diagnostic Path (PDTA) shared between 2 bone specialists (BSs), 9 GPs, as reference treaters, and a multidisciplinary group of 25 specialists of the Province of Pavia was defined. The strategic directions of the two largest public hospitals in Pavia have supported the PDTA, which was validated by the quality departments of the hospitals themselves. Finally, sixty GPs belonging to the network have joined the PDTA. This model is the first example of integrated management between hospitals and out-of-hospital healthcare services for the primary and secondary prevention of fragility fractures (FF), where the GPs play a pivotal role as managers and supervisors to ensure proper care to chronic patients according to their levels of severity

Constrained viscous sintering of melting grains

\ua9 2023 The Author(s). Viscous sintering of food grains can occur spontaneously and cause undesired caking or be induced to drive a change in food product structure. The dynamics of this phenomenon are still poorly understood, particularly when the sintering is coupled with heat or mass transfer. The aim of this work is to investigate experimentally the effects of heat transfer and grain size on the sintering dynamics of partially melting fat-based food products, i.e., dark chocolate. Two spherical particles were heated through forced convection using an air stream at different temperatures and velocities. Optical and IR thermal cameras were employed to capture the bridge growth and surface temperature evolution. Subsequently, the optical images were analysed to extract the evolution of the size of the bridge between the grains and a first order kinetics model was used to describe the sintering dynamics. The experimental observation showed that the viscous sintering is faster for smaller spheres, and at higher air flow temperature and velocity. When the spheres are heated from ambient conditions, a lag time is observed, which was found to be related to the time required by the material to reach a temperature at which its viscosity decreases to about 54 Pa\ub7s allowing flow. Therefore, the lag time is temperature-dependent and decreases with decreasing particle size and increasing air temperature and velocity. Moreover, a semiempirical model involving a temperature dependent viscosity was proposed to describe the viscous coalescence. It is shown that considering some correction parameters accounting for the experimental conditions leads to an accurate prediction of the bridge growth. The model could be incorporated into the discrete element method to simulate the viscous sintering of a bulk of chocolate grains

Wicking in a powder.

We investigate the wicking in granular media by considering layers of grains at the surface of a liquid and discuss the critical contact angle below which spontaneous impregnation takes place. This angle is found to be on the order of 55° for monodisperse layers, significantly smaller than 90°, the threshold value for penetrating assemblies of tubes. Owing to geometry, impregnating grains is more demanding than impregnating tubes. We also consider the additional effects of polydispersity and pressure on this wetting transition and discuss the corresponding shift observed for the critical contact angle