Prognostic Role of sST2 in Acute Heart Failure and COVID-19 Infection—A Narrative Review on Pathophysiology and Clinical Prospective

The importance of cardiovascular biomarkers in clinical practice increased dramatically in the last years, and the interest extends from the diagnosis purpose to prognostic applications and response to specific treatment. Acute heart failure, ischemic heart failure, and COVID-19 infection represent different clinical settings that are challenging in terms of the proper prognostic establishment. The aim of the present review is to establish the useful role of sST2, the soluble form of the interleukin-1 receptor superfamily (ST2), physiologically involved in the signaling of interleukin-33 (IL-33)-ST2 axis, in the clinical setting of acute heart failure (HF), ischemic heart disease, and SARS-CoV-2 acute infection. Molecular mechanisms associated with the IL33/ST2 signaling pathways are discussed in view of the clinical usefulness of biomarkers to early diagnosis, evaluation therapy to response, and prediction of adverse outcomes in cardiovascular diseases.     

Molecular and Histological Effects of Glyphosate on Testicular Tissue of the Lizard Podarcis siculus

The expansion of agriculture produces a steady increase in habitat fragmentation and degradation due to the increased use of pesticides and herbicides. Habitat loss and alteration associated with crop production play an important role in reptile decline, among which lizards are particularly endangered. In this study, we evaluated testicular structure, steroidogenesis, and estrogen receptor expression/localization after three weeks of oral exposure to glyphosate at 0.05 and 0.5 μg/kg body weight every other day in the field lizard Podarcis siculus. Our results show that glyphosate affected testicular morphology, reduced spermatogenesis, altered gap junctions and changed the localization of estrogen receptors in germ cells, increasing their expression; the effects were mostly dose-dependent. The result also demonstrates that glyphosate, at least at these concentrations, did not influence steroidogenesis. Overall, the data indicate that this herbicide can disturb the morphophysiology of the male lizard’s reproductive system, with obviously detrimental effects on their reproductive fitness. The effects of glyphosate must be considered biologically relevant and could endanger the reproductive capacity not only of lizards but also of other vertebrates, including humans; a more controlled and less intensive use of glyphosate in areas devoted to crop production would therefore be advisable.     

Pivotal Role of Inflammation in Celiac Disease

Celiac disease (CD) is an immune-mediated enteropathy triggered in genetically susceptible individuals by gluten-containing cereals. A central role in the pathogenesis of CD is played by the HLA-restricted gliadin-specific intestinal T cell response generated in a pro-inflammatory environment. The mechanisms that generate this pro-inflammatory environment in CD is now starting to be addressed. In vitro study on CD cells and organoids, shows that constant low-grade inflammation is present also in the absence of gluten. In vivo studies on a population at risk, show before the onset of the disease and before the introduction of gluten in the diet, cellular and metabolic alterations in the absence of a T cell-mediated response. Gluten exacerbates these constitutive alterations in vitro and in vivo. Inflammation, may have a main role in CD, adding this disease tout court to the big family of chronic inflammatory diseases. Nutrients can have pro-inflammatory or anti-inflammatory effects, also mediated by intestinal microbiota. The intestine function as a crossroad for the control of inflammation both locally and at distance. The aim of this review is to discuss the recent literature on the main role of inflammation in the natural history of CD, supported by cellular fragility with increased sensitivity to gluten and other pro-inflammatory agents.     

KRAS: A Druggable Target in Colon Cancer Patients

Mutations in KRAS are among the most frequent aberrations in cancer, including colon cancer. KRAS direct targeting is daunting due to KRAS protein resistance to small molecule inhibition. Moreover, its elevated affinity to cellular guanosine triphosphate (GTP) has made the design of specific drugs challenging. Indeed, KRAS was considered ‘undruggable’. KRASG12C is the most commonly mutated variant of KRAS in non-small cell lung cancer. Currently, the achievements obtained with covalent inhibitors of this variant have given the possibility to assess the best therapeutic approach to KRAS-driven tumors. Mutation-related biochemical assets and the tissue of origin are expected to influence responses to treatment. Further attempts to obtain mutant-specific KRAS (KRASG12C) switch-II covalent inhibitors are ongoing and the results are promising. Drugs targeted to block KRAS effector pathways could be combined with direct KRAS inhibitors, immunotherapy or T cell-targeting approaches in KRAS-mutant tumors. The development of valuable combination regimens will be essential against potential mechanisms of resistance that may arise during treatment.     

Ensuring the reliability of electron beam crosslinked electric cables by the optimization of the dose depth distribution with Monte Carlo simulation

The reliability of electric cables and wires using electron beam crosslinked polymers as isolator materials strongly depends on the accuracy in predicting the dose deposited during irradiation. This paper presents the main reliability issues that can be encountered in field operation, experimental data showing the criticality of the dose parameter, and proposes the use of a built-in reliability approach based on Monte Carlo simulation to design optimum processing conditions. The main requirements and advantages of the Monte Carlo based methodology are discussed in conjunction with the limitations of the traditional heuristic calculation procedure. Finally, Monte Carlo simulation is used for the first time to point out some relevant effects that occur during processing and that can lead to severe dose estimation errors.     

Early Stage Automatic Strategy for Power-Aware Signal Processing Systems Design

Complexity management, portability and long term adaptivity are common challenges in different fields of embedded systems, normally colliding with the needs of efficient resource utilization and power balance. Image/signal processing systems, though required to offer a large variety of complex functions, have also to deal with battery-life limitations. Wearable signal processing systems, for example, should provide high performance and support new generation standards without compromising their portability and their long-term usability. These constraints challenge hardware designers: early stage trade-off analysis and power management automated techniques are helpful to guarantee a reasonable time-to-market. In the field of video codec specifications, the MPEG standard known as Reconfigurable Video Coding (RVC) framework addresses functional complexity and adaptivity leveraging on the intrinsic modularity of the dataflow model of computation, but it still lacks in offering power management support. The main contribution of this work is providing an automatic early-stage power management methodology to be adopted within the MPEG-RVC context. Starting from different high-level specifications, our mapping methodology identifies directly on the high-level models disjointed homogeneous logic clock regions, where the platform resources can be enabled/disabled together without affecting the overall system performance. To extend its usability to the RVC community, we have integrated this methodology within the Multi-Dataflow Composer (MDC) tool. MDC is a tool for on-the-fly reconfigurable signal processing platforms deployment. In this paper, we extended MDC to address power-aware multi-context systems. To prove the effectiveness of our work, a coprocessor for image and video processing acceleration has been assembled. This latter has been synthesized on a 90 nm ASIC technology, where demonstrated up to 90 % of reduction in the dynamic power consumption on different dataflow-intensive applications. The coprocessor has been implemented also on FPGA, confirming, partially, the benefits of adopting the proposed methodology.     

A Markov model for blind image separation by a mean-field EM algorithm.

This paper deals with blind separation of images from noisy linear mixtures with unknown coefficients, formulated as a Bayesian estimation problem. This is a flexible framework, where any kind of prior knowledge about the source images and the mixing matrix can be accounted for. In particular, we describe local correlation within the individual images through the use of Markov random field (MRF) image models. These are naturally suited to express the joint pdf of the sources in a factorized form, so that the statistical independence requirements of most independent component analysis approaches to blind source separation are retained. Our model also includes edge variables to preserve intensity discontinuities. MRF models have been proved to be very efficient in many visual reconstruction problems, such as blind image restoration, and allow separation and edge detection to be performed simultaneously. We propose an expectation-maximization algorithm with the mean field approximation to derive a procedure for estimating the mixing matrix, the sources, and their edge maps. We tested this procedure on both synthetic and real images, in the fully blind case (i.e., no prior information on mixing is exploited) and found that a source model accounting for local autocorrelation is able to increase robustness against noise, even space variant. Furthermore, when the model closely fits the source characteristics, independence is no longer a strict requirement, and cross-correlated sources can be separated, as well.     

ECCE: Enhanced cooperative channel establishment for secure pair-wise communication in wireless sensor networks

This paper presents the ECCE protocol, a new distributed, probabilistic, cooperative protocol to establish a secure pair-wise communication channel between any pair of sensors in a wireless sensor network (WSN). The main contributions of the ECCE protocol are: to allow the set-up of a secure channel between two sensors (principals) that do not share any pre-deployed key. This feature is obtained involving a set of sensors (cooperators) in the channel establishment protocol; to provide probabilistic authentication of the principals as well as the cooperators. In particular, the probability for the attacker to break authentication check decreases exponentially with the number of cooperators involved; to trade off the memory space required to store the pre-deployed encryption keys with the number of cooperators involved in the protocol. Hence, memory storage can be used to store keys built with the ECCE protocol, which helps amortizing the (limited) overhead incurred in the ECCE key set-up; to be adaptive to the level of threat the WSN is subject to. We provide analytical analysis and extensive simulations of ECCE, which show that the proposed solution increases both the probability of a secure channel set-up and the probability of channel resilience with respect to other protocols.     

Pharmacokinetics and Pharmacodynamics of Anthocyanins after Administration of Tart Cherry Juice to Individuals with Gout

Scope

Tart cherries (TCs) contain high levels of anthocyanins that exert potent antioxidant and antiinflammatory effects and potentially benefit individuals with gout.

Methods and results

This study aims to quantitate the major anthocyanins in TC Juice Concentrate (TCJC) and identify the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of the major anthocyanin cyanidin-3-glucosylrutinoside (C3GR). A PK-PD study enrolling human subjects with a history of gout is performed. Subjects are randomized to receive either 60 or 120 mL of TCJC. Anthocyanins are quantitated using liquid chromatography-mass spectroscopy (LCMS). Antioxidant and antiinflammatory mRNA expression is measured using real-time qPCR before and after the administration of TCJC. A population PK model (popPK) is fit to the experimental data, and an indirect PD model (IDR) is constructed in Monolix.

Conclusion

Of the bioavailable anthocyanins, C3GR achieves the highest plasma concentration in a dose-dependent manner. A popPK predicts anthocyanin exposure, and an IDR produces reasonable approximations of PD effects.