At the last meeting of the European Society of Cardiology (ESC) in 2019 the new version of the ESC guidelines on "Diabetes, prediabetes and cardiovascular diseases", which were written in ...collaboration with the European Association for the Study of Diabetes (EASD), were presented. The recommendations of these guidelines included the novel evidence generated over the last 6 years in large cardiovascular outcome trials with novel antidiabetic drugs. This led to a completely novel positioning of medications for lowering blood glucose levels in the reduction of cardiovascular events for patients with diabetes mellitus. This overview article summarizes the most important recommendations of these new guidelines.
Fuel cell technology is not widely used in the transportation industry because of its cost and technical and scientific barriers, which limit its efficiency, reliability and durability. Multi-stack ...fuel cell (MFC) systems could provide an improvement in performance over usual fuel cell systems. The aim of this paper is to present the current state of the art of multi-stack fuel cell systems.
Different electrical and fluidic architectures have been designed for MFC systems. The effects of these architectures on the performances of the system are presented. Depending on the chosen architecture, a more reliable system is obtained through the enabling of degraded mode operation. The research focus is analyzed, and the remaining challenges are presented.
•Multi-stack systems offer interests for efficiency and reliability improvements.•Different electrical, fluidic and thermal configurations for ancillaries are depicted.•Impacts of multi-stack fuel cell architectures on the performances are detailed.•DC–DC converter architecture for multi-stack systems are compared.•Remaining challenges in the investigation of MFC system are presented.
Abstract Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. ...The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3 weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium. However, in 10 week old db/db−/− mice, a model of diabetes and obesity, sitagliptin potently reduced plasma glucose rise in peritoneal glucose tolerance tests and reduced weight increase. The myocardium of untreated db/db−/− mice exhibited a marked increase of the phosphorylation of AMPK, ACC, TSC2, expression of p53 and fatty acid translocase (FAT/CD36) membrane expression. These changes were reduced by DPP-4 inhibition. Sitagliptin showed no effect on cardiomyocyte size but prevented myocardial fibrosis in the 10 week old db/db−/− mice and reduced expression of TGF-β1, markers of oxidative stress and the accumulation of advanced glycation end products in cardiomyocytes. Working heart analyses did not show an effect of sitagliptin on parameters of systolic cardiac function. In animals with diabetes and obesity, sitagliptin improved glucose tolerance, reduced weight gain, myocardial fibrosis and oxidative stress. Furthermore the study provides evidence that treatment with sitagliptin decreases elevated myocardial fatty acid uptake and oxidation in the diabetic heart. These observations show beneficial myocardial metabolic effect of DPP-4 inhibition in this mouse model of diabetes and obesity.
Due to the anthropogenic pressures of expansion areas for livestock and agricultural production in the Brazilian Cerrado, it is of paramount importance to understand the dynamics of land use/land ...cover (LULC) changes in this region. Thus, we investigated LULC changes in two sub-basins of the Tocantins-Araguaia River basin from 1997 to 2015 and consequently projected future changes for the timespan between 2030 and 2050. The Formoso sub-basin experienced significant expansion of agricultural and pasture areas, whereas the Sono sub-basin limited farmland expansion (more stable native vegetation) due to substantial protected areas, trends that were also observed for future projections (2030 and 2050). Pastureland in the Formoso sub-basin increased by 5.8%, while the Sono sub-basin saw significant gains in cultivated land, according to change detection analyses during the 1997–2015 period. High stability probabilities of no change (> 70%) for grassland areas in the Sono River sub-basin and pasturelands in the Formoso River sub-basin were computed. The CA–Markov model demonstrated a high consistency level with actual LULC classes for both sub-basins, as indicated by an overall Kappa coefficient above 0.8. Future projections for 2030 and 2050 show a substantial expansion of agriculture and pasture in both sub-basins, driven by specific factors such as soil organic carbon stocks, distance from rural settlements, and proximity to rivers. Short- and mid-term simulations indicate substantial expansion of agriculture and pasture in both basins, with potential adverse impacts on water erosion. Consequently, developing policies for soil management and sustainable land use planning is essential for agroecosystem sustainability, promoting a balanced approach to economic development while addressing climate change and anthropogenic challenges.
Diabetes mellitus is an important comorbidity in patients with heart failure. The presence of heart failure in diabetes worsens the prognosis of patients. Recent studies suggest that appropriate ...diagnostic approaches followed by differential medical treatment are of crucial importance to improve patient outcomes. This article summarizes important aspects of the association between diabetes mellitus and heart failure.
Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as ...monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 10
PFU/mL on day 1 (cycle 1), 10
PFU/mL on day 22 (cycle 2), and 10
PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.
The ultrashear viscometer (USV) has been adapted and employed to investigate the permanent shear thinning of polystyrene solutions in a series of phthalate ester base fluids. The permanent shear ...stability index based on viscosities measured at 10
6
s
−1
, PSSI(10
6
), has been found to be a convenient way to express the magnitude of permanent shear thinning. When comparing permanent shear thinning at various shear rates in the USV, it is very important to take account of the different times of shear that are present at different shear rates. The PSSI(10
6
) value divided by the total time of shear is then a useful way of quantifying and comparing permanent shear thinning rates. Tests using polystyrene in different viscosity base fluids have shown that this rate of permanent shear thinning depends on shear stress and not shear rate and varies linearly with polymer concentration. The rate of permanent shear thinning also varies exponentially with shear stress, suggestive of a stress-promoted polymer breakdown process. By using a small volume of test fluid in the USV and solvent extraction after a test, it has proved possible to obtain molecular weight distributions of polymer after shear using gel permeation chromatography (GPC). This indicates that the polymer breakdown process is different at low and high polymer concentrations, with molecule fragmentation at low polymer concentration but mid-chain scission at high concentration. A key feature of the USV is that, unlike other methods currently used to measure permanent shear thinning behaviour of engine oils, it subjects the test fluid to well-defined, controllable high shear conditions. Coupled with the use of GPC, this makes it possible for the first time to relate quantitatively the permanent shear thinning of engine oils to shear conditions and to polymer degradation response.
Aims/hypothesis
Inhibitors of dipeptidyl peptidase-IV (DPP-IV), such as sitagliptin, increase glucagon-like peptide-1 (GLP-1) concentrations and are current treatment options for patients with type 2 ...diabetes mellitus. As patients with diabetes exhibit a high risk of developing severe atherosclerosis, we investigated the effect of sitagliptin on atherogenesis in
Apoe
−/−
mice.
Methods
Apoe
−/−
mice were fed a high-fat diet and treated with either sitagliptin or placebo for 12 weeks. Plaque size and plaque composition were analysed using Oil Red O staining and immunohistochemistry. Furthermore, in vitro experiments with the modified Boyden chamber and with gelatine zymography were performed to analyse the effects of GLP-1 on isolated human monocyte migration and metalloproteinase-9 (MMP-9) release.
Results
Treatment of
Apoe
−/−
mice with sitagliptin significantly reduced plaque macrophage infiltration (the aortic root and aortic arch both showing a 67% decrease;
p
< 0.05) and plaque MMP-9 levels (aortic root showing a 69% and aortic arch a 58% reduction; both
p
< 0.01) compared with controls. Moreover, sitagliptin significantly increased plaque collagen content more than twofold (aortic root showing an increase of 58% and aortic arch an increase of 73%; both
p
< 0.05) compared with controls but did not change overall lesion size (8.1 ± 3.5% vs 5.1 ± 2.5% for sitagliptin vs controls;
p
= NS). In vitro, pretreatment of isolated human monocytes with GLP-1 significantly decreased cell migration induced by both monocyte chemotactic protein-1 and by the protein known as regulated on activation, normal T cell expressed and secreted (RANTES) in a concentration-dependent manner. Furthermore, GLP-1 significantly decreased MMP-9 release from isolated human monocyte-derived macrophages.
Conclusions/interpretation
Sitagliptin reduces plaque inflammation and increases plaque stability, potentially by GLP-1-mediated inhibition of chemokine-induced monocyte migration and macrophage MMP-9 release. The effects observed may provide potential mechanisms for how DPP-IV inhibitors could modulate vascular disease in high-risk patients with type 2 diabetes mellitus.
Different two-dimensional (2D) and three-dimensional (3D) imaging techniques are used for procedure planning and selection of prosthesis size before transcatheter aortic valve implantation. This ...study sought to compare different 2D and 3D imaging techniques and determine the accuracy of 3D transoesophageal echocardiography (TEE) for accurate analysis of aortic annulus dimensions.
In 49 consecutive patients with severe aortic stenosis undergoing transcatheter aortic valve implantation angiography, 2D transthoracic echocardiography (TTE), 2D and 3D TEE, and dual-source CT (DSCT) were performed to determine aortic annulus diameters. TTE and 2D TEE provided only one diameter of the aortic annulus. Angiography, DSCT and 3D TEE allowed measurement of diameters in sagittal and coronal views. The distance between aortic annulus and left main coronary artery ostium was measured by angiography, DSCT and 3D TEE.
Sagittal diameters determined by angiography, TTE, 2D TEE, 3D TEE and DSCT were smaller than coronal diameters determined by angiography, 3D TEE and DSCT. Coronal and sagittal diameters determined by 3D TEE were in high agreement with corresponding measurements by DSCT (23.60±1.89 vs 23.46±2.07 mm and 22.19±1.96 vs 22.27±2.01 mm, respectively; mean±SD). There was a high correlation between DSCT and 3D TEE for the definition of coronal and sagittal aortic annulus diameters (r=0.88, SEE=0.89 mm and r=0.77, SEE=1.26 mm, respectively). Correlation of 3D TEE (13.47±1.67 mm) and DSCT (13.64±1.82 mm) in the analysis of the distance between aortic annulus and left main coronary artery ostium was better (r=0.54, SEE=1.55 mm) than between angiography (14.85±3.84 mm) and DSCT (r=0.35, SEE=1.77 mm).
3D imaging techniques should be used to evaluate aortic annulus diameters, as 2D imaging techniques, providing only a sagittal view, underestimate them. 3D TEE provides measurements of aortic annulus diameters similar to those obtained by DSCT.
Efferocytosis, the clearing of dead or dying cells from living tissues, is a highly programmed, vital process to maintain the healthy functioning of every organism. Disorders of efferocytosis have ...been linked to several chronic diseases including atherosclerosis and auto-immune diseases. To date several different assays to determine phagocytosis, using microscopy or FACS analysis with labelled targets, have been developed. However, many of these are unable to differentiate between cells that have truly been phagocytosed and those still present on the surface of the macrophages hindering exact assessment of efferocytotic capacity. We herein describe AnxA5-pHrodo and its negative control M1234-pHrodo as new molecular probes to measure in vitro as well as ex-vivo efferocytotic capacity.
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