Search

Background: Atrial fibrillation (AF) is associated with chronic inflammation, a hallmark of ageing process. The aim of this study was to determine interleukin-6 (IL-6)-associated variables, also exploring acylcarnitines, expression of mitochondrial abnormalities. Methods: We evaluated 22 controls and 50 patients with persistent AF. IL-6 and acylcarnitines were measured with ELISA kits and mass spectrometry techniques. Results: IL-6 concentration (mean: 3.9 ± 3.1 pg/mL) was lower in controls and increased in AF patients, especially with heart failure. The CHA2DS2-VASc, the MMSE and the SPPB scores were 3.8 ± 1.6, 28 ± 2 and 9.4 ± 2.1. Thirteen acylcanitines correlated with IL-6. At multivariable analysis, IL-6 was directly associated with C4-OH—a short-chain acylcarnitine, fibrinogen and alanine aminotransferase values, and with hyperuricemia. An inverse association existed with calcium concentration and SPPB score. Conclusions: In older AF patients, IL-6 correlated with acylcarnitines and lower physical performance. Alterations in energy production, reduced physical function and inflammation could contribute to frailty development.

Recent medical advancements have increased life expectancy, leading to a surge in patients affected by multiple chronic diseases and consequent polypharmacy, especially among older adults. This scenario increases the risk of drug interactions and adverse drug reactions, highlighting the need for medication review and deprescribing to reduce inappropriate medications and optimize therapeutic regimens, with the ultimate goal to improving patients’ health and quality of life. This position statement from the Italian Scientific Consortium on medication review and deprescribing aims to describe key elements, strategies, tools, timing, and healthcare professionals to be involved, for the implementation of medication review and deprescribing in different healthcare settings (i.e., primary care, hospital, long-term care facilities, and palliative care). Challenges and potential solutions for the implementation of medication review and deprescribing are also discussed.

The hierarchical self-assembly of various lipophilic guanosines exposing either a phenyl or a ferrocenyl group in the C(8) position was investigated. In a solution, all the derivatives were found to self-assemble primarily into isolated guanine (G)-quartets. In spite of the apparent similar bulkiness of the two substituents, most of the derivatives form disordered structures in the solid state, whereas a specific 8-phenyl derivative self-assembles into an unprecedented, cation-free stacked G-quartet architecture.

This is a 57–year–old male patient suffering from multiple cardiovascular risk factors: obesity, arterial hypertension, dyslipidemia, type 2 diabetes mellitus, active smoker. Chronic obstructive pulmonary disease. Stage 2 chronic kidney disease. Peripheral vascular disease with previous bilateral thromboendarterectomy and percutaneous revascularization of the lower limbs. Stable angina for which three years ago he underwent Coronary Artery Bypass Graft: left internal mammary artery (LIMA) to left anterior descending artery combined with saphenous vein grafts to the main obtuse marginal branch. The patient presented with Acute Coronary Syndrome non ST–segment elevation myocardial infarction (N–STEMI), intermittent episodes of chest pain due to mild exertion in the previous days. Antero–lateral ST depression and inverted T waves, associated with a mild reduction in left ventricular systolic function due to hypokinesia of the antero–lateral walls and increased troponin values were present. Coronary angiography documented patency of the LIMA graft without evidence of any culprit lesions on the coronary branches. However, selective angiography documented a sub–occlusion of the proximal left subclavian artery (Figure 1). A computed tomography scan confirmed a hyperdense calcified plaque occluding 95% of the origin of the left subclavian artery. The patient then underwent angioplasty with stenting of the left subclavian artery (Figure 2). Subclavian coronary steal syndrome usually presents with exertional angina, but rarely can cause Acute Coronary Syndrome. During coronary angiography performed for Acute Coronary Syndrome and in the absence of detection of clear coronary culprit lesions, selective angiography of the subclavian artery may confirm the suspicion of coronary steal syndrome.

γ-Glutamyltransferase (GGT) is an enzyme that uses γ-glutamyl compounds as substrates and catalyzes their transfer to a water molecule or an acceptor substrate with varied physiological function in bacteria, plants, and animals. Crystal structures of GGT are known for different species and in different states of the chemical reaction; however, the structural dynamics of the substrate binding to the catalytic site of GGT are unknown. Here, we modeled Escherichia coliGGT’s glutamine binding by using a swarm of accelerated molecular dynamics (aMD) simulations. Characterization of multiple binding events identified three structural binding motifs composed of polar residues in the binding pocket that govern glutamine binding into the active site. Simulated open and closed conformations of a lid-loop protecting the binding cavity suggest its role as a gating element by allowing or blocking substrates entry into the binding pocket. Partially open states of the lid-loop are accessible within thermal fluctuations, while the estimated free energy cost of a complete open state is 2.4 kcal/mol. Our results suggest that both specific electrostatic interactions and GGT conformational dynamics dictate the molecular recognition of substrate–GGT complexes.

ABSTRACTIn this paper, a rectangular aerostatic bearing with multiple supply holes is optimised with a multiobjective optimisation approach. The design variables taken into account are the supply holes position, their number and diameter, the supply pressure, while the objective functions are the load capacity, the air consumption and the stiffness and damping coefficients. A genetic algorithm is applied in order to find the Pareto set of solutions. The novelty with respect to other optimisations which can be found in literature is that number and location of the supply holes is completely free and not associated to a pre-defined scheme. A vector x associated with the supply holes location is introduced in the design parameters and given in input to the optimizer.

In this paper, a rectangular aerostatic bearing with multiple supply holes is optimised with a multiobjective optimisation approach. The design variables taken into account are the supply holes position, their number and diameter, the supply pressure, while the objective functions are the load capacity, the air consumption and the stiffness and damping coefficients. A genetic algorithm is applied in order to find the Pareto set of solutions. The novelty with respect to other optimisations which can be found in literature is that number and location of the supply holes is completely free and not associated to a pre-defined scheme. A vector x associated with the supply holes location is introduced in the design parameters and given in input to the optimizer.

We report the gelation propensity of three gelators derived from l-dihydroxyphenylalanine (l-Dopa), where the amino group is derivatized with three different fatty acids (lauric acid, palmitic acid, and azelaic acid). The long aliphatic side chains should introduce additional van der Waals interactions among the molecules, contributing to the self-assembly process. The hydrogels have been prepared with the pH change method, and both the hydrogels and the corresponding aerogels have been analyzed using several techniques. In any case, Lau-Dopa provides stronger hydrogels compared with the other gelators. This property may be ascribed to its tendency to efficiently form supramolecular β-sheet structures, as outlined by the ECD, IR, and SEM analyses. Moreover, the preliminary measurement of the apparent pKadisplays for Lau-Dopa two plateaux, as previously observed for, one at about pH 12 and a second one at pH 7.5. Thus, its pKaresults in two apparent pKashifts of ∼8.5 and ∼4 pH units above the theoretical pKa, as a consequence of a multistep self-assembly pathway that correlates, in the final β-sheet-based hydrogel, with a high degree of order and stability.

•Different from “7 + 3” combination, CPX-351 prevents mucosal damage, dysbiosis, and morbidity in preclinical intestinal inflammatory settings.•CPX-351 protects via the aryl hydrocarbon receptor–IL-22-IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes.

The experimental charge density distribution of two new iodoperfluoroalkylimidazole derivatives has been determined with the aspherical atom model against single-crystal X-ray diffracted intensities and analyzed by means of the Bader Quantum Theory of Atoms In Molecules. The compounds self-assemble in the solid state forming infinite chains through strong I···N halogen bonds. The topological and energetic features of these interactions have been determined and compared with those of a previously reported I···N interaction formed by an iodoperfluoroarene derivative, allowing elucidation of the role of hybridization of the carbon atom bonded to the halogen atom in the nature of the halogen bonding interaction. The weaker interactions present in the crystal structures have been investigated as well, with particular attention to F···F interactions. They have also been analyzed through the Interacting Quantum Atoms approach in order to elucidate their role in stabilizing the crystal structure.

This paper is focused on the measurement of both dielectric and magnetic characteristics of a penetrable material at radio frequency through a time‐domain reflectometry probe. The goal is to prove that a time‐domain reflectometry probe can offer the possibility to discriminate the dielectric permittivity from the magnetic permeability of the material. This is due to the fact that the time‐domain reflectometry datum depends both on the propagation velocity of the electromagnetic waves in the probed medium and on the intrinsic impedance of the probe. However, the possibility to attain such a clear discrimination is bound by the condition that the reflection coefficient is measured (or calculated) along the probe at the air–soil interface in the frequency domain. Generally, time‐domain reflectometry probes measure the total (incident plus reflected) field in the time domain, and subsequently, the datum is needed to meet the condition that such claimed purpose is not just the Fourier transform of a datum collected by means of a common time‐domain reflectometry probe. Rather, either a devoted hardware should be implemented or a very accurate knowledge of the incident field should be guaranteed in order to separate the reflected wave from the incident one. In this preliminary work, our study has been restricted to a theoretical investigation in the frequency domain. In particular, our focus is set on the lossless case, and the attention is devoted to the issue of possible multiple solutions to demonstrate that this obstacle can be overcome by making the frequency step narrower or, alternatively, by narrowing the length step of the probe. Simulation results based on a bifilar transmission line model are shown.

We consider the problem of uncertainty quantification analysis of the output of underground flow simulations. We consider in particular fractured media described via the discrete fracture network model; within this framework, we address the relevant case of networks in which the geometry of the fractures is described by stochastic parameters. In this context, due to a possible lack of smoothness in the quantity of interest with respect to the stochastic parameters, well assessed techniques such as stochastic collocation may fail in providing reliable estimates of first-order moments of the quantity of interest. In this paper, we overcome this issue by applying the Multilevel Monte Carlo method, using as underlying solver an extremely robust method. Addressing uncertainty in geometry of fracture networksFlow simulations on stochastic discrete fracture networksMultilevel Monte Carlo method for uncertainty quantification in underground simulations

Lepidium meyenii(Walp.), commonly called maca, is an Andean crop belonging to the Brassicaceae family. Maca hypocotils are habitually consumed as customary food as well as traditional remedies for pathological conditions such as infertility. Moreover, the characterization of maca extracts revealed the presence of compounds that are able to modulate the nervous system. Aimed to evaluate the efficacy of L. meyeniiin persistent pain, the present study analyzed the effects of a commercial root extract from maca in different animal models reproducing the most common causes of chronic painful pathologies. A qualitative characterization of this commercial extract by high performance liquid chromatography-mass spectrometry and tandem mass spectrometry analyses allowed us to confirm the presence of some macamides known as bioactive constituents of this root and the absence of the main aromatic glucosinolates. The acute oral administration of maca extract is able to reduce mechanical hypersensitivity and postural unbalance induced by the intra-articular injection of monoiodoacetate and the chronic-constriction injury of the sciatic nerve. Furthermore, L. meyeniiextract reverts pain threshold alterations evoked by oxaliplatin and paclitaxel. A good safety profile in mice and rats was shown. In conclusion, the present maca extract could be considered as a therapeutic opportunity to relieve articular and neuropathic pain.