Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients’ exposure to gliflozins’ treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.     

Chloride-induced steel corrosion in alkali-activated fly ash mortar: Increased propensity for corrosion initiation at defects

Chloride contents at the steel–mortar interface that initiate steel corrosion were determined for carbon steel in alkali-activated fly ash mortar for three different exposure conditions: exposure to 1 M NaCl solution; leaching in deionized water and then exposure to 1 M NaCl solution; and leaching in deionized water, aging in air at 20°C and natural CO₂ concentration, and then exposure to 1 M NaCl solution. For comparison, a Portland cement mortar, exposed to 1 M NaCl solution, was studied. The median values of the corrosion-initiating chloride contents (average over the full length of the rebar) in the alkali-activated fly ash mortar varied between 0.35 and 1.05 wt% Cl with respect to binder, consistently lower than what was obtained for the Portland cement mortar, but with no clear trend regarding the exposure conditions. For most of the alkali-activated fly ash mortar specimens, preferential corrosion at the connection between the working electrode and the external measurement setup was observed, while preferential corrosion did not occur for the Portland cement mortar. Scanning electron microscopy and auxiliary experiments in synthetic solutions indicated that this behavior was caused by inhomogeneities at the steel–mortar interface in the alkali-activated mortar, likely due to its peculiar rheological properties in the fresh state.     

GPU-based parallel vertex substitution algorithm for the p-median problem

We introduce a GPU-based parallel vertex substitution (pVS) algorithm for the p-median problem using the CUDA architecture by NVIDIA. pVS is developed based on the best profit search algorithm, an implementation of vertex substitution (VS), that is shown to produce reliable solutions for p-median problems. In our approach, each candidate solution in the entire search space is allocated to a separate thread, rather than dividing the search space into parallel subsets. This strategy maximizes the usage of GPU parallel architecture and results in a significant speedup and robust solution quality. Computationally, pVS reduces the worst case complexity from sequential VS’s O(p · n²) to O(p · (n ? p)) on each thread by parallelizing computational tasks on GPU implementation. We tested the performance of pVS on two sets of numerous test cases (including 40 network instances from OR-lib) and compared the results against a CPU-based sequential VS implementation. Our results show that pVS achieved a speed gain ranging from 10 to 57 times over the traditional VS in all test network instances.     

Alcohol-aversion therapy: Relation between strength of aversion and abstinence.

Assessed the degree of alcohol aversion in 60 alcoholics (aged 21–60 yrs) who received emetic alcohol-aversion therapy. Based on prior aversion-therapy research, it was predicted that aversion therapy would result in the following changes in response to alcoholic, but not to nonalcoholic, flavors: (1) decreased consumption in taste tests, (2) more negative flavor ratings, (3) overt behavioral indicants of aversion (e.g., grimacing), and (4) increased tachycardic response. A positive correlation between posttreatment tachycardic response to alcohol and number of days to the first drink was also predicted. Results support these predictions. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stepwise periodic distillation—I: Total reflux operation

The theoretical predictions of doubled overall efficiency for plate distillation columns operated in the controlled cycling mode have not been confirmed by pilot scale experiments. In an attempt to circumvent the hydrodynamic problems causing this failure, we have found a new periodic operating mode where the liquid flow is manipulated directly, and not indirectly through pulsations of the vapour flow rate (as in controlled cycling).In this paper we present the theory of stepwise periodic distillation, under assumptions allowing a comparison with known results for controlled cycling. We show that the two processes have the same asymptotic efficiencies for large values of the number of trays while periodic stepwise distillation is slightly more efficient than controlled cycling for a finite number of trays     

The effect of B‐doping on the electrical conductivity of polymer‐derived Si(B)OC ceramics

In this work the room temperature electrical conductivity of Si(B)OC glasses made via polymer pyrolysis at 1200°C and 1400°C (maximum temperature) and having different amount of boron was measured. When B content is increased from zero (pure SiOC glass) up to B/Si=0.5 the electrical conductivity increases in 2 orders of magnitude from 4.09±0.64×10^?5 up to 2.93±1.91×10^?3 with a corresponding decrease in the activation energy from about 1.08 to 0.51 eV. This results shows for the first time that the electrical conductivity of Si‐based polymer‐derived ceramics can be controlled by the amount of the doping element. The structure of the Si(B)OC glasses has been studied with different techniques including FT‐IR, XRD and Raman spectroscopy. The Raman study indicates that B partially substitutes C into the sp² C planes of the free carbon phase forming trigonal BC₃ units. Accordingly, the evolution of the electrical properties with the B content has been correlated with the corresponding structural evolution and a hypothesis is presented to rationalize the role of boron on the electrical conductivity of SiOBC glasses.     

A Peltier cell calorimeter for the direct measurement of the isothermal entropy change in magnetic materials

We developed a calorimetric technique to measure the isothermal magnetocaloric entropy change. The method consists in the use of Peltier cells as heat flow sensor and heat pump at the same time. In this paper, we describe the setup, the constitutive equations of the Peltier cell as sensor and actuator, and the calibration procedure. The Peltier heat is used to keep the sample isothermal when magnetic field is changed. The temperature difference between the sample and the thermal reservoir is kept by a digital control within 5 mK for a magnetic field rate of 20 mT s(-1). The heat flux sensitivity around 1 microW. With this method, it is possible to measure the magnetocaloric effect in magnetic materials by tracing the curves of the exchanged entropy Delta(e)s as a function of the magnetic field H. The method proves to be, in particular, suitable to reveal the role of the entropy production Delta(i)s, which is connected with hysteresis. Measurement examples are shown for Gd, BaFe(12)O(19) ferrite, and Gd-Si-Ge.     

Instructional compensation for age-related cognitive declines: Effects of goal specificity in maze learning.

The differential effects of goal specificity on maze learning among 40 young adults and 40 old adults were investigated. Participants had to navigate through a computerized training-maze task. The finish point of the maze could be presented either as a specific location or in more general terms. After solving the maze problem participants were required to solve the same problem again, either by moving from start to finish or backward from finish to start. The hypotheses that the presence or absence of a specific goal would disproportionately compromise or enhance, respectively, elderly people's performance were confirmed. Although young adults outperformed old participants in all conditions, these differences were much smaller in the nonspecific goal conditions. These results suggest that instruction based on cognitive load theory (J. Sweller, J. J. G. Van Merri?nboer, & F. Paas, 1998) can compensate for age-related cognitive declines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A little thanks goes a long way: Explaining why gratitude expressions motivate prosocial behavior.

Although research has established that receiving expressions of gratitude increases prosocial behavior, little is known about the psychological mechanisms that mediate this effect. We propose that gratitude expressions can enhance prosocial behavior through both agentic and communal mechanisms, such that when helpers are thanked for their efforts, they experience stronger feelings of self-efficacy and social worth, which motivate them to engage in prosocial behavior. In Experiments 1 and 2, receiving a brief written expression of gratitude motivated helpers to assist both the beneficiary who expressed gratitude and a different beneficiary. These effects of gratitude expressions were mediated by perceptions of social worth and not by self-efficacy or affect. In Experiment 3, we constructively replicated these effects in a field experiment: A manager's gratitude expression increased the number of calls made by university fundraisers, which was mediated by social worth but not self-efficacy. In Experiment 4, a different measure of social worth mediated the effects of an interpersonal gratitude expression. Our results support the communal perspective rather than the agentic perspective: Gratitude expressions increase prosocial behavior by enabling individuals to feel socially valued. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An incentive for coordination in a decentralised service chain with a Weibull lifetime distributed facility

This article deals with a decentralised service chain consisting of a service provider and a facility owner. The revenue allocation and service price are, respectively, determined by the service provider and the facility owner in a non-cooperative manner. To model this decentralised operation, a Stackelberg game between the two parties is formulated. In the mathematical framework, the service system is assumed to be driven by Poisson customer arrivals and exponential service times. The most common log-linear service demand and Weibull facility lifetime are also adopted. Under these analytical conditions, the decentralised decisions in this game are investigated and then a unique optimal equilibrium is derived. Finally, a coordination mechanism is proposed to improve the efficiency of this decentralised system.