Zero Emission Geothermal Flash Power Plant

The successful exploitation of geothermal energy for power production relies on the availability of nearly zero emission and efficient technologies. Two zero emission flash plant layouts, with full reinjection of the geothermal fluid (non-condensable gas included), are considered. This paper focusses on the CO2issue, and therefore only the carbon dioxide is considered as non-condensable gas present in the geothermal fluid; the CO2 flow is separated, compressed, and reinjected with the geothermal fluid. Both the reservoir and the power plant are simulated. A first scheme of plant presents a conventional layout in which the CO2is separated and compressed after the condenser. The second scheme presents a plant layout that allows the separation of the CO2at higher pressure with respect to the conventional layout, thus reducing the requested power consumption. The conventional plant scheme performs always better at higher temperature and at lower concentration of CO2. The new layout results better for low temperature and higher gas content

Emergency transapical mitral valve-in-valve implantation for bioprosthesis failure: Transapical implantation of an Edwards Sapien-XT in a dysfunctional mitral bioprosthesis in a critical patient

Background: Valve-in-Valve (VIV) Transcatheter Aortic Valve Replacement (TAVR) is now the treatment of choice in high-surgical-risk patients with failing aortic bioprosthesis. Although less performed, VIV-Transcatheter Mitral Valve Replacement (TMVR) is a valid treatment option for selected high-risk patients with degenerated mitral bioprostheses. Several cases of elective ViV- TAVR and -TMVR have been reported but only few were performed in critical hemodynamic conditions. Case presentation: We report the case of a patient underwent balloon-expandable transapical mitral valve-in-valve implantation in an emergency setting due to a severe stenosis of a bioprosthesis in mitral position. The procedure was successfully performed, with no residual mitral regurgitation or paravalvular leaks, and uneventful. Conclusion: Transcatheter transapical mitral valve-in-valve implantation could represent a feasible and effective strategy even in critical setting

SKPDB: a structural database of shikimate pathway enzymes

<p>Abstract</p> <p>Background</p> <p>The functional and <b>s</b>tructural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans.</p> <p>Description</p> <p>The ShiKimate Pathway DataBase (SKPDB) is a relational database applied to the study of shikimate pathway enzymes in microorganisms and plants. The current database is updated regularly with the addition of new data; there are currently 8902 enzymes of the shikimate pathway from different sources. The database contains extensive information on each enzyme, including detailed descriptions about sequence, references, and structural and functional studies. All files (primary sequence, atomic coordinates and quality scores) are available for downloading. The modeled structures can be viewed using the Jmol program.</p> <p>Conclusions</p> <p>The SKPDB provides a large number of structural models to be used in docking simulations, virtual screening initiatives and drug design. It is freely accessible at <url>http://lsbzix.rc.unesp.br/skpdb/</url>.</p

Changes in body composition in early breast cancer patients treated with aromatase inhibitors

Purpose The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).Methods This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors.Results A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively.Conclusion Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients

A real-life study of daratumumab-bortezomib-dexamethasone (D-VD) in lenalidomide exposed/refractory multiple myeloma patients: a report from the Triveneto Myeloma Working Group

Treatment of lenalidomide refractory (Len-R) multiple myeloma (MM) patients still represents an unmet clinical need. In the last years, daratumumab-bortezomib-dexamethasone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial. This real-life study aimed to evaluate the efficacy and safety of the D-VD regimen in a cohort that exclusively enrolled Len exposed or refractory MM patients. The study cohort included 57 patients affected by relapsed/refractory MM. All patients were previously exposed to Len, with 77.2% being refractory. The overall response rate (ORR) was 79.6% with 43% of cases obtaining at least a very good partial response (VGPR). The D-VD regimen showed a favorable safety profile, with low frequency of grade 3–4 adverse events, except for thrombocytopenia observed in 21.4% of patients. With a median follow-up of 13 months, median progression-free survival (PFS) was 17 months. No significant PFS differences were observed according to age, ISS, LDH levels, type of relapse, and high-risk FISH. Len exposed patients displayed a PFS advantage as compared to Len refractory patients (29 vs 16 months, p = 0.2876). Similarly, patients treated after Len maintenance showed a better outcome as compared to patients who had received a full-dose Len treatment (23 vs 13 months, p = 0.1728). In conclusion, our real-world data on D-VD combination showed remarkable efficacy in Len-R patients, placing this regimen as one of the standards of care to be properly taken into account in this MM setting

Exergetic performance and comparative assessment of bottoming power cycles operating with carbon dioxide–based binary mixture as working fluid

This paper presents CO2-toluene (CO2-C7H8) binary mixture as working fluid to enhance the energetic and exergetic performance of CO2 bottoming power cycles in warm ambient conditions. A criterion for selection of CO2-based binary mixture is defined, and 0.9 CO2/0.1 C7H8 composition is decided based on the required minimum cycle temperature compatible with ambient conditions. Bottoming simple regenerative cycle (BSRC) and bottoming preheating cycle (BPHC) configurations are selected, and their realistic operating conditions are determined based on sensitivity analysis. The performance of bottoming cycles using CO2-C7H8 binary mixture is compared with the bottoming cycles using pure CO2 as working fluid at different ambient temperatures. It is observed that the cycles operating with pure CO2 can only perform better at lower ambient temperature conditions, whereas, at the increased ambient temperatures, bottoming cycles with CO2-C7H8 binary mixture outperform and produce significant gains in exergetic and energetic performance compared with pure CO2 bottoming cycles. A maximum gain of exergetic efficiency for BSRC and BPHC observed is 26.83% and 18.71%, respectively, at an operating ambient temperature of 313 K, whereas an overall gain in energetic efficiencies for BSRC and BPHC observed is 28.92% and 10.12%, respectively. Taking into consideration thermodynamic performance, overall UA (product of overall heat transfer coefficient and heat transfer area for the heat exchanger) and specific investment cost, BPHC configuration is suggested as reasonable choice for higher ambient temperature conditions

Abnormal DNA Methylation Induced by Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells

Background CD 34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be "memorized" by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord-blood-derived CD 34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal-cell-derived factor 1 alpha and reduced protein and mRNA expression of the C-X-C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high-glucose CD 34+ stem cells that negatively correlated with mRNA expression (Pearson r=-0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high-glucose CD 34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD 34+ stem cells "memorize" the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration

Impact of Fractional Flow Reserve Derived from Coronary Computed Tomography Angiography on Heart Team Treatment Decision-Making in Patients with Multivessel Coronary Artery Disease: Insights from the SYNTAX III REVOLUTION Trial

Background: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFRCT) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFRCT on heart team's treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. Methods: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFRCT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFRCT changed the treatment decision and planning. Results: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFRCT analysis in 88%. FFRCT was available for 1030 lesions (mean FFRCT value 0.64\ub113). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFRCT. The addition of FFRCT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFRCT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. Conclusions: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFRCT changed heart team's treatment decision-making and procedural planning in one-fifth of the patients