What is new in valvular heart disease ESC Guidelines 2021?

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Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

Earnings management techniques in the context of Italian unlisted firms

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Aerated Buffalo Slurry Improves Spinach Plant Growth and Mitigates CO2 and N2O Emissions from Soil

Manure management is the main strategy for mitigating gas emissions from livestock farming. In this study, a laboratory-scale experiment was set up to identify suitable conditions to be applied in a farm-scale experiment. The liquid fraction (LF) of slurry was aerobically treated and greenhouse gas emissions from soil were evaluated. Furthermore, the value of treated LF as a fertilizer on spinach plants was also tested. The aeration of LF determined an increase in mean alkalinity due to ammonia loss. The mass fraction of heavy metals also decreased, likely due to the reduction in solubility. After being applied on soil, aerated LF determined lower CO2 and N2O emissions compared to untreated LF due to a reduced nitrogen load. Spinach plants fertilized with treated LF showed a lush growth and exhibited a lower heavy metal mass fraction as well as a higher content of antioxidants compared to plants fertilized with untreated slurry. Our results show that aeration might be an effective alternative for slurry management as it is able to produce an eco-friendly final product with a high fertilizing value

Development of an Electric-Driven Smart Window Model for Visual Comfort Assessment

Smart windows, especially those electric-driven, represent one of the most advanced technologies for controlling solar radiation. For a correct use, it is necessary to understand their real behaviour through in-situ measurements on full-scale application as well as calibrating and validating visual simulation models capable of predicting their performances. In this paper, the preliminary results of current research activities aimed at developing simulation models of electric-driven full-scale glazing are presented. The research activities started with the assessment of the visible solar transmittance as a function of light incident angle through in-situ measurements; different models, with related values, of the visible solar transmittance were considered. For each simulation model, the corresponding transmittance value was set in the RADIANCE “trans” material model and the simulated illuminance values, for a defined acquisition point of a test-facility, were then compared with the experimental data. Finally, for each model, indoor luminance distributions were reported considering a typical office seating position. Preliminary results, based on the in-situ measurements approach, highlighted a sufficient accuracy for one of the models adopted; further analyses are needed in order to upgrade the simulation models available and assess the effective performances of these windows

The receptor-type protein tyrosine phosphatase J antagonizes the biochemical and biological effects of RET-derived oncoproteins.

Abstract Thyroid cancer is frequently associated with the oncogenic conversion of the RET receptor tyrosine kinase. RET gene rearrangements, which lead to the generation of chimeric RET/papillary thyroid carcinoma (PTC) oncogenes, occur in PTC, whereas RET point mutations occur in familial multiple endocrine neoplasia type 2 (MEN2) and sporadic medullary thyroid carcinomas (MTC). We showed previously that the expression of the receptor-type protein tyrosine phosphatase J (PTPRJ) is suppressed in neoplastically transformed follicular thyroid cells. We now report that PTPRJ coimmunoprecipitates with wild-type RET and with the MEN2A-associated RET(C634R) oncoprotein but not with the RET/PTC1 and RET-MEN2B isoforms. Using mutated forms of PTPRJ and RET-MEN2A, we show that the integrity of the respective catalytic domains is required for the PTPRJ/RET-MEN2A interaction. PTPRJ expression induces dephosphorylation of the RET(C634R) and, probably via an indirect mechanism, RET/PTC1 oncoproteins on two key RET autophosphorylation sites (Tyr1062 and Tyr905). This results in a significant decrease of RET-induced Shc and extracellular signal-regulated kinase 1/2 phosphorylation levels. In line with this finding, adoptive PTPRJ expression reduced the oncogenic activity of RET(C634R) in an in vitro focus formation assay of NIH3T3 cells. As expected from the coimmunoprecipitation results, the RET(M918T) oncoprotein, which is associated to MEN2B and sporadic MTC, was resistant to the dephosphorylating activity of PTPRJ. Taken together, these findings identify RET as a novel substrate of PTPRJ and suggest that PTPRJ expression levels may affect tumor phenotype associated with RET/PTC1 and RET(C634R) mutants. On the other hand, resistance to PTPRJ may be part of the mechanism of RET oncogenic conversion secondary to the M918T mutation. (Cancer Res 2006; 66(12): 6280-7

Enhancing behavioural changes: a narrative review on the effectiveness of a multifactorial APP-based intervention integrating physical activity

The rapid evolution of technologies is a key innovation in the organisation and management of physical activities (PA) and sports. The increase in benefits and opportunities related to the adoption of technologies for both the promotion of a healthy lifestyle and the management of chronic diseases is evident. In the field of telehealth, these devices provide personalised recommendations, workout monitoring and injury prevention. The study aimed to provide an overview of the landscape of technology application to PA organised to promote active lifestyles and improve chronic disease management. This review identified specific areas of focus for the selection of articles: the utilisation of mobile APPs and technological devices for enhancing weight loss, improving cardiovascular health, managing diabetes and cancer and preventing osteoporosis and cognitive decline. A multifactorial intervention delivered via mobile APPs, which integrates PA while managing diet or promoting social interaction, is unquestionably more effective than a singular intervention. The main finding related to promoting PA and a healthy lifestyle through app usage is associated with "behaviour change techniques". Even when individuals stop using the APP, they often maintain the structured or suggested lifestyle habits initially provided by the APP. Various concerns regarding the excessive use of APPs need to be addressed

Heme Oxygenase-1 and Brain Oxysterols Metabolism Are Linked to Egr-1 Expression in Aged Mice Cortex, but Not in Hippocampus

Throughout life, stress stimuli act upon the brain leading to morphological and functional changes in advanced age, when it is likely to develop neurodegenerative disorders. There is an increasing need to unveil the molecular mechanisms underlying aging, in a world where populations are getting older. Egr-1 (early growth response 1), a transcriptional factor involved in cell survival, proliferation and differentiation – with a role also in memory, cognition and synaptic plasticity, can be implicated in the molecular mechanism of the aging process. Moreover, Heme Oxygenase-1a (HO), a 32 kDa heat-shock protein that converts heme to iron, carbon monoxide and biliverdin, is a key enzyme with neuroprotective properties. Several in vitro and in vivo studies reported that HO-1 could regulate the metabolism of oxysterols, oxidation products of cholesterol that include markers of oxidative stress. Recently, a link between Egr-1 and HO-1 has been demonstrated in mouse lung cells exposed to cigarette smoke. In view of these data, we wanted to investigate whether Egr-1 can be implicated also in the oxysterol metabolism during brain aging. Our results show that Egr-1 expression is differently expressed in the cortex and hippocampus of old mice, as well as the oxysterol profile between these two brain areas. In particular, we show that the cortex experiences in an age-dependent fashion increasing levels of the Egr-1 protein, and that these correlate with the level of HO-1 expression and oxysterol abundance. Such a situation was not observed in the hippocampus. These results are further strenghtened by our observations made with Egr-1 KO mice, confirming our hypothesis concerning the influence of Egr-1 on oxysterol production and accumulation via regulation of the expression of HO-1 in the cortex, but not the hippocampus, of old mice. It is important to notice that most of the oxysterols involved in this process are those usually stimulated by oxidative stress, which would then represent the triggering factor for this mechanism

high performance microwave waveguide devices produced by laser powder bed fusion process

Abstract Additive manufacturing technologies are currently envisaged to boost the development of a next generation of microwave devices intended for satellite telecommunications. Due to their excellent electromagnetic and mechanical properties, metal waveguide components are key building blocks of several radio frequency (RF) systems used in these applications. This article reports the perspectives deriving from the use of laser powder bed fusion (L-PBF) technology to the production of high-performance microwave waveguide devices. A robust design of filters has been implemented in several prototypes manufactured in AlSi10Mg alloy. The corresponding measured performance confirm the applicability of the L-PBF process to the intended application

Rat protein tyrosine phosphatase η physically interacts with the PDZ domains of syntenin

AbstractThe tyrosine phosphatase r-PTPη is able to suppress the malignant phenotype of rat thyroid tumorigenic cell lines. To identify r-PTPη interacting proteins, a yeast two-hybrid screening was performed and an insert corresponding to the full-length syntenin cDNA was isolated. It encodes a protein containing two PDZ domains that mediates the binding of syntenin to proteins such as syndecan, proTGF-α, β-ephrins and neurofascin. We show that r-PTPη is able to interact with syntenin also in mammalian cells, and although syntenin is a tyrosine-phosphorylated protein it is not a substrate of r-PTPη. The integrity of both PDZ domains of syntenin and the carboxy-terminal region of r-PTPη are required for the interaction between syntenin and r-PTPη