OPTIMIZED PROCEDURE TO EVALUATE THE THERMAL ENERGY TRANSFER IN HEMODIALYSIS TREATMENT

Hemodialysis treatment is biased by complications during its operative phases. One of these potential accidents consists in intradialytic hypotension, that causes discomfort to the patient and may even increase the risk of death. Therefore, it is very important to predict these events in routine clinical procedures. A cause of hypotension may be thermal energy/heat exchanges between extracorporeal system and the surrounding environment. A model to evaluate these heat losses is proposed and improved in order to maintain constant patient blood temperature. A convenient procedure is defined to improve and optimize clinical treatment. Although most hemodialysis machines automatically control the dialysate solution temperature starting from peripheral body temperature measurements, the proposed method is based on the control of the pre-dialysis core temperature of the patient, and the temperature of the blood entering the artery from the extracorporeal circuit after the treatment in the dialyzer. Measurements of arterial and venous blood temperatures are obtained in a non invasive way by a suitable estimate of the thermal energy exchanges between the blood and the environment during the extracorporeal recirculation. The suggested model guarantees a constant core temperature of the patient, improving prevention from intradialytic hypotension.     

Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.     

A simulative approach for evaluating alternative feeding scenarios in a kanban system

In accordance with the lean production philosophy, an assembly line may be supplied by means of a kanban system, which regulates and simplifies the flow of materials between the lines and the warehouses. This paper focuses on evaluation of feeding policies that differ from each other in term of the number of kanbans managed per feeding tour. A pure cost-based approach is thus proposed, which considers both inline inventories along with handling costs proportionate to the number of operators involved in the parts-feeding process. A multi-scenario simulative approach is applied in order to establish the number of operators required to avoid inline shortages. The scenario minimising total cost is then selected. The innovation introduced is a model for describing kanban arrivals and their requests for feeding, improving the potential of the simulation to describe real-life environments. Lastly, a case study from the automotive industry is presented in order to highlight the applicability of the proposed approach as well and the effects of alternative feeding policies on the total cost incurred.     

Implementation and evaluation of an Asbru-based decision support system for adjuvant treatment in breast cancer

The domain of cancer treatment is a promising field for the implementation and evaluation of a protocol-based clinical decision support system, because of the algorithmic nature of treatment recommendations. However, many factors can limit such systems’ potential to support the decision of clinicians: technical challenges related to the interoperability with existing electronic patient records and clinical challenges related to the inherent complexity of the decisions, often collectively taken by panels of different specialists. In this paper, we evaluate the performances of an Asbru-based decision support system implementing treatment protocols for breast cancer, which accesses data from an oncological electronic patient record. Focusing on the decision on the adjuvant pharmaceutical treatment for patients affected by early invasive breast cancer, we evaluate the matching of the system's recommendations with those issued by the multidisciplinary panel held weekly in a hospital.     

Pressure-induced pH changes in aqueous solutions - On-line measurement and semi-empirical modelling approach

The main aim of this work is to investigate the effect of CO₂ and N₂O under pressure in aqueous solution - both on-line and in real-time. In particular, the paper presents the kinetics of pH behaviour of either slightly buffered minimal medium (MM) or non-buffered solution (Ringer solution) during high-pressure treatment at 5, 30 and 60 bar at 25 °C.An innovative spectrophotometric approach has been developed: an optical fiber conducted the inlet signal of a light source into the high-pressure reactor, while another fiber conducted the outlet signal to a spectrometer, thus, obtaining measurements on-line and real-time.CO₂ treatment resulted in a pH decrease down to 3.0 in Ringer solution with the equilibrium being reached after 800 s, while the slightly buffered MM allows only for a decrease down to 4.5 with equilibrium being reached after slightly more than 40 s at 60 bar.N₂O treatment, as expected, did not lead to any acidification of the treated medium at any conditions tested.Furthermore, a mathematical model describing both the solubilization kinetics of CO₂ and in aqueous solution and the decrease of extracellular pH has been implemented. This model may easily be applied to different reactor configurations. The theoretical results and the goodness of the fit has been verified using the experimental results showing a good accuracy of the complex phenomena with a simplification that is of vital relevance for technical processes.     

Conjugation of amino-bioactive glasses with 5-aminofluorescein as probe molecule for the development of pH sensitive stimuli-responsive biomaterials

Bioceramics, such as silica-based glasses, are widely used in bone and teeth restoration. Nowadays, the association between nanotechnology and pharmacology is one of the most promising research fields in cancer therapy. The advanced processing methods and new chemical strategies allow the incorporation of drugs within them or on their functionalized surfaces. Bioceramics can act as local drug delivery systems to treat bone and teeth diseases. The present paper reports data related to the development of a pH-stimuli responsive bioactive glass. The glass conjugation with 5-aminofluorescein (5-AF), through a pH-sensitive organic spacer, allows to produce a pH-responsive bioactive biomaterial: when it is exposed to specific pH changes, it can favour the release of 5-AF directly at the target site. 5-AF has been chosen as a simple, low cost, non toxic model to simulate doxorubicin, an anticancer drug. As doxorubicin, 5-AF contains an amino group in its structure in order to form an amide bond with the carboxylic functionalities of the glass. Raman spectroscopy and thermal analysis confirm the glass conjugation of 5-AF by means of an amide bond; the amount of 5-AF loaded was very high (≈65 and 44 wt%). The release tests at two different pH (4.2 and 7.4) show that the amount of released 5-AF is higher at acid pH with respect to physiological one. This preliminary datum evidenced that a pH-sensitive drug delivery system has been developed. The low amount of 5-AF released (<1 wt% of the total 5-AF) is due to the very low solubility of 5-AF in aqueous medium. This disadvantage, may be overcome in a dynamic environment (physiological conditions), where it is possible to obtain a drug release system ensuring an effective therapeutic dose for long times and, at the same time, avoiding the drug toxicity.     

Sorption of propylene and propane in polyurethane membranes containing silver nanoparticles

The preparation of a facilitated transport membrane of polyurethane (PU) containing silver nanoparticles is reported. The propylene and propane sorption was investigated aiming at the selective separation from C3s mixtures. The silver particles were photogenerated in situ into the polyurethane matrix using UV light radiation and silver triflate (AgCF₃SO₃) as precursor. The morphological properties of these membranes (PUAg) reveled great dispersion of silver particles, which size was smaller than 110 nm. The propylene solubility in PUAg resulted more than four times superior to the one for the pure PU membrane, revealing the high affinity between silver and propylene. Flory–Huggins theory was more accurate to describe the propylene sorption behavior in PUAg than Henry's model. The ideal solubility selectivity of PUAg membrane resulted 24.4, indicating that there is a good potential for an industrial application aiming at the separation of propylene/propane. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42916.     

Potent and Selective Non‐hydroxamate Histone Deacetylase 8 Inhibitors

Specific inhibition of histone deacetylase 8 (HDAC8) has been suggested as a promising option for the treatment of neuroblastoma and T‐cell malignancies. A novel class of highly potent and selective HDAC8 inhibitors with a pyrimido[1,2‐c][1,3]benzothiazin‐6‐imine scaffold was studied that is completely different from the traditional concept of HDAC inhibitors comprising a zinc binding group (ZBG), in most cases a hydroxamate group, a spacer, and a capping group that may interact with the surface of the target protein. Although lacking a ZBG, some of the new compounds were shown to have outstanding potency against HDAC8 in the single‐digit nanomolar range. The pyrimido[1,2‐c][1,3]benzothiazin‐6‐imines also inhibited the growth of solid and hematological tumor cells. The small size and beneficial physicochemical properties of the novel HDAC inhibitor class underline the high degree of drug likeness. This and the broad structure–activity relationship suggest great potential for the further development of compounds with the pyrimido[1,2‐c][1,3]benzothiazin‐6‐imine scaffold into innovative and highly effective therapeutic drugs against cancer.