24 Gliflozins and ventricular function in patients affected by chronic heart failure with diabetes mellitus

Abstract Aims Diabetes is the most common comorbidity of HF patients. SGLT2 inhibitors has been shown to reduce hospitalization in patients with HF. The cardioprotective mechanisms of gliflozines have not been elucidated. The aim of our study was to evaluate the effect of SGLT2 inhibitors on right and left ventricular function in T2DM patients with HF. Methods and results One hundred and fifteen consecutive outpatients with CHF and T2DM were screened in the Daunia Heart Failure Registry. Seventy-eight of them were enrolled and followed up between May 2019 and September 2020. All patients underwent conventional, TDI and strain echocardiography in an ambulatory setting, at the beginning and after 3 months of therapy with SGLT2 inhibitors. Seventy-eight consecutive outpatients with CHF and T2DM (mean age 67.4 ± 8.4 years, male: 83%) were enrolled in the study. Thirty-eight of them started the treatment with SGLT2 inhibitors, while the remaining forty continued their original therapy. After 3 months of therapy, LVEF, LVEDD, and LVESD statistically improved (respectively, from 39.68 ± 7.78% to 45.08 ± 9.04%, P: 0.001 and 57.32 ± 9.76 mm to 54.16 ± 6.54 mm, P: 0.01 and from 47.51 ± 1.58 mm to 43.24 ± 8.12, P: 0.0008). Changes in left ventricular function and dimensions were not significant in patients who did not started a therapy with SGLT2 inhibitors. There was a statistically significant reduction of E/E′ (from 16.51 ± 22.55 to 9.73 ± 3.35, P: 0.0007) in patients with treatment with SGLT2i. Moreover, there was an improvement of right ventricular function, due to a statistically significant reduction of PAPs and increase of TAPSE (respectively, from 30.63 ± 8.80 to 24.00 ± 8.35, P: 0.008; from 19.16 ± 2.54 to 21.18 ± 2.84, P: 0.0003) and S′ (10.42 ± 2.09 to 12.91 ± 2.50, P: 0.000) 3 months after the administration of SGLT2 inhibitors therapy vs. the control group. Conclusions In a real-world scenario, our results showed that the treatment with SGLT-2 inhibitors in patients with CHF and diabetes is associated with an echocardiographic biventricular function improvement

Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B.

Background & aims In chronic HBV infection, mitochondrial functions and proteostasis are dysregulated in exhausted HBV-specific CD8 T cells. To better characterise the potential involvement of deregulated protein degradation mechanisms in T cell exhaustion, we analysed lysosome-mediated autophagy in HBV-specific CD8 T cells. Bioactive compounds able to simultaneously target both mitochondrial functions and proteostasis were tested to identify optimal combination strategies to reconstitute efficient antiviral CD8 T cell responses in patients with chronic HBV infection. Methods Lysosome-mediated degradation pathways were analysed by flow cytometry in virus-specific CD8 T cells from patients with chronic HBV infection. Mitochondrial function, intracellular proteostasis, and cytokine production were evaluated in HBV-peptide-stimulated T cell cultures, in the presence or absence of the polyphenols resveratrol (RSV) and oleuropein (OLE) and their metabolites, either alone or in combination with other bioactive compounds. Results HBV-specific CD8 T cells from patients with CHB showed impaired autophagic flux. RSV and OLE elicited a significant improvement in mitochondrial, proteostasis and antiviral functions in CD8 T cells. Cytokine production was also enhanced by synthetic metabolites, which correspond to those generated by RSV and OLE metabolism in vivo, suggesting that these polyphenols may also display an effect after transformation in vivo. Moreover, polyphenolic compounds improved the T cell revitalising effect of mitochondria-targeted antioxidants and of programmed cell death protein 1/programmed cell death ligand 1 blockade. Conclusions Simultaneously targeting multiple altered intracellular pathways with the combination of mitochondria-targeted antioxidants and natural polyphenols may represent a promising immune reconstitution strategy for the treatment of chronic HBV infection. Lay summary In chronic hepatitis B, antiviral T lymphocytes are deeply impaired, with many altered intracellular functions. In vitro exposure to polyphenols, such as resveratrol and oleuropein, can correct some of the deregulated intracellular pathways and improve antiviral T cell function. This effect can be further strengthened by the association of polyphenols with antioxidant compounds in a significant proportion of patients. Thus, the combination of antioxidants and natural polyphenols represents a promising strategy for chronic hepatitis B therapy

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis

Investigation and Optimization of Disk-Laser Welding of 1 mm Thick Ti-6Al-4V Titanium Alloy Sheets

Ti-6Al-4V joints are employed in nuclear engineering, civil industry, military, and space vehicles. Laser beam welding has been proven to be promising, thanks to increased penetration depth and reduction of possible defects of the welding bead; moreover, a smaller grain size in the fusion zone is better in comparison to either TIG or plasma arc welding, thus providing an increase in tensile strength of any welded structures. In this frame, the regression models for a number of crucial responses are discussed in this paper. The study has been conducted on 1 mm thick Ti-6Al-4V plates in square butt welding configuration; a disk-laser source has been used. A three-level Box-Behnken experimental design is considered. An optimum condition is then suggested via numerical optimization with the response surface method using desirability functions with proper weights and importance of constraints. Eventually, Vickers microhardness testing has been conducted to discuss structural changes in fusion and heat affected zone due to welding thermal cycles

Electrical discharge machining of René 108 DS nickel superalloy for aerospace turbine blades

AbstractManufacturing industries aim for high quality production with decreased cost and time. To this purpose, optimization of the processing parameters is required, in order to reduce the machining time and match the quality standards. This study has been conducted to electrical discharge machining on Renè 108 DS. In the process, the electrode material is crucial for metal removal and tool wear, whose optimization usually leads to conflicting goals. Therefore, two electrode materials, graphite (Poco EDM-3) and copper-infiltrated-graphite (Poco EDM-C3) have been tested in a factorial plan including current, voltage, duty cycle and electrode polarity. The process is discussed in terms of material removal rate, tool wear rate, wear ratio and final surface roughness of the work-piece

Enhancing Physical Activity with Immersive Virtual Reality:A Systematic Review

The aim of this article is to review how immersive virtual reality-enhanced physical activity (IVR-PA) can be used to improve psychological, physiological, and performance outcomes linked to exercising and to compare it with non-immersive virtual reality-enhanced physical activity (nIVR-PA) and with traditional physical activity (TR-PA). We also aimed to explore the effectiveness of IVR-PA in promoting psychological well-being and engagement in physical activity. A systematic literature review (Prospero CRD42022330572) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. OVID (including Medline, Embase, GlobalHealth, and APA PsychInfo), Web of Science, and Sport Discuss were searched. The quality of the studies was assessed using the Effective Public Health Practice Project Quality Assessment. The search identified 26,548 titles. After screening, 20 studies (the total number of participants was 798) published between 2009 and 2023 were included in this systematic review. The quality of the studies was rated as weak (n = 9), moderate (n = 10), or strong (n = 1). Overall, the reviewed studies indicated that, compared with TR-PA and nIVR-PA, IVR-PA was associated with an increase in enjoyment of physical activity, a reduction in perceived exertion, and increased rates of self-efficacy, intrinsic motivation, and exercise intention. Furthermore, some studies showed higher muscular strength and aerobic increase after an IVR-PA intervention compared with TR-PA. The findings suggest that IVR-PA can improve psychological, physiological, and performance outcomes linked to exercising, as well as improving psychological well-being and engagement in physical activity. However, owing to the methodological limitations of the reviewed studies, further research is encouraged.</p

Designing Sustainable Scenarios. Natural-based Coatings as a Barrier to Oil and Grease in Food Paper Packaging

Cellulose materials are widely used in food packaging. Paper-based packaging, intended to be in contact with food, require specific properties to ensure food safety. In order to obtain greaseproof paper, packaging industry commonly uses mechanical treatments, surface coatings, or otherwise paper can be coupled with aluminum and polymeric films. In many cases these processes compromise food packaging recyclability. The renewed interest in the development of sustainable packaging solutions, together with the increasing environmental standards and laws, speed up the research of CIPACK - Interdepartmental Centre for Packaging to the exploration of innovative natural-based coatings as barrier to oil and grease. Experimental tests, conducted in the laboratories of the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” - Politecnico di Milano, confirmed the good repellent properties of the natural-based coatings. After laboratory analysis, possible applications for the developed treatments were investigated: compostable food containers represent a sustainable alternative to common packaging used for frozen food, ready-to-eat meals or fast food

Back to nature: novel solutions to enhance food packaging sustainability

Commonly employed in food packaging, cellulosic materials are characterized by a biodegradable nature. Produced from renewable resources, paper-based materials can be evaluated as recyclable and biodegradable products. Nevertheless, the level of biodegradability of cellulose-based packaging depends on the substances and processes used to functionalize it. In order to use cellulosic materials in direct contact with food, indeed, paperpackaging industry concentrates its studies and researches on increasing barrier properties. Usually, cellulose-based packaging need to be functionalized through mechanical treatments, surface coatings, or by coupling paper with aluminum and polymeric films. These traditional surface treatments present disadvantages in terms of sustainability: they cause environmental problems due to materials recycling and recovering process. Papers used as primary food packaging could not be recycled, as food particles contaminate the paper recycling process, and should not be treated for composting because of the presence of non-biodegradable substances as coatings. For this reason, nowadays, the attention on minimizing environmental impact has prompted designers’ research to find more sustainable solutions for food pack. Teaching behaviour change on materials consumption in food packaging introduces to a wide range of design issues, including performance and aesthetic properties, sustainability, and food compatibility. Today, the challenge of food packaging industry is the development of new packaging materials, compatible with food, biodegradable or compostable, and realized with renewable resources. In the laboratories of the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” (at Politecnico di Milano), the good results obtained by testing some natural-based coatings, developed by the researchers of CIPACK (Interdepartmental Centre for Packaging) and applied to paperboard materials, let imagine novel scenarios of application in food packaging. Compostable food containers, made of cellulosic materials functionalized by the cited coatings, represent a sustainable alternative to pack, for example, ready-to-eat meals or fast food products. Moreover, this research opens to a new idea of food packaging: a system where packaging meets market criteria in terms of performance and cost, is designed to be functional and safe, is made using renewable resources, and at the end of its life cycle, as the food contained, could be degraded without leaving contaminants in the environment. The design and science-based approaches used in this study allow communicating a positive environmental vision for paper packaging used for food contact applications

Ceramic aerogels from TEMPO-oxidized cellulose nanofibre templates: Synthesis, characterization, and photocatalytic properties

Aerogels are highly porous materials whose interesting chemico-physical properties can be exploited in several advanced applications. Ceramic aerogels based on titanium oxides, allow coupling the physical properties with the photocatalytic role of TiO2 in promoting pollutant photodegradation, selective organic photosynthesis, and antibacterial activity. Here, we prepared hybrid organic-ceramic aerogels via one-pot approach by mixing aqueous hydrogels of cellulose nanofibres with TiO2 or TiO2/SiO2 sols and subsequent freeze-drying of the obtained mixtures. The further calcination of the hybrid materials at suitable temperatures allowed achieving ceramic aerogels able to combine a pronounced adsorption efficiency of organic molecules with photocatalytic activity. The new materials have been characterized in terms of morphology, structure, and heterogeneous photo-degradation ability of potential pollutants. A possible explanation for the different behavior in adsorption affinity and photocatalytic efficiency is reported on the basis of the experimental evidences