Search Results (76)

Background: Antithrombotic therapy plays an important role in acute coronary syndrome (ACS). The combination of anticoagulant and antiplatelet therapy resulted in fewer complications and stronger potency compared to traditional monotherapy. Our net meta-analysis aimed to compare and rank the safety of different treatments used in patients with ACS. Method: We conducted a search for trials in three prominent databases. The main objective of our investigation was to assess hemorrhage. Additional outcomes included mortality, myocardial infarction, stroke, and embolism. We used a frequentist network meta-analysis with a random-effects model to, directly and indirectly, compare safety across different antithrombotic strategies. Result: A total of 30 randomized clinical trials were included in this net meta-analysis with 135,471 ACS patients. In these eight different antithrombotic therapies, SAPT (single-agent platelet inhibitor therapy) showed the lowest risk of bleeding (SUCRA = 0.5%). The highest risk of bleeding was observed in VKA (vitamin K antagonists) + DAPT (dual antiplatelet therapy) (SUCRA = 99.8%). Bleeding among NOAC (non-vitamin K antagonist oral anticoagulants) + DAPT was found to be higher than DAPT (OR = 1.94, 95% CI = 1.42–2.65). NOAC + SAPT significantly reduced the embolism (OR = 1.50, 95% CI = 1.16–1.94) and myocardial infarction (OR = 1.22, 95% CI = 1.08–1.37) events compared with SAPT. In addition, VKA significantly reduced the rate of stroke compared with SAPT (OR = 3.45, 95% CI = 1.17–10.18). However, no significant difference was observed in death events among these eight antithrombotic therapies. Conclusions: We advise against the use of SAPT in ACS due to its elevated risk of embolism, myocardial infarction, and stroke. It is important to mention that the combination of NOAC and SAPT has a lower incidence of myocardial infarction, bleeding and embolism problems. Therefore, the combination of NOAC and SAPT may be the optimal approach to achieve a balance between the risks of bleeding and embolism. This meta-analysis was registered in PROSPERO with the registration number CRD42024542826. Full article

Lactic acid (LA) is a high-value chemical with growing demand for the production of polymers and plastics and in the food and pharmaceutical industries. However, production costs remain a significant constraint when using conventional food-grade substrates. This study investigates Ivorian sugarcane molasses, an abundant agro-industrial by-product, as a low-cost carbon source for LA production via batch fermentation with Limosilactobacillus fermentum ATCC 9338. Molasses was pretreated by acid hydrolysis to improve fermentability, increasing glucose and fructose concentrations. Comparative fermentations using raw and pretreated molasses showed a 75% increase in LA production (32.4 ± 0.03 g/L) after pretreatment. Optimisation using Box–Behnken design revealed that the initial sugar concentration, inoculation rate, and stirring speed significantly influenced lactic acid production. Under optimal conditions, a maximum LA concentration of 52.4 ± 0.49 g/L was achieved with a yield of 0.95 g/g and productivity of 0.73 g/L·h. Kinetic analysis confirmed efficient sugar utilisation under the optimised conditions, and polarimetry revealed a near-racemic lactic acid. A simplified cost analysis showed that molasses could reduce carbon source costs by over 70% compared to refined sugars, supporting its economic viability. This work demonstrates the potential of pretreated molasses under robust fermentation conditions as a sustainable and cost-effective substrate for LA production in resource-limited contexts. The approach aligns with circular bioeconomy principles and presents a replicable model for decentralised bioproduction in a developing country like Côte d’Ivoire. Full article

Introduction: Antiplatelet therapy (APT) increases bleeding risk and is frequently used in patients who undergo percutaneous dilatational tracheostomy (PDT). However, there are different techniques for single-step PDTs, which can be differently invasive. The aim of the present study was to investigate complications in patients undergoing PDT while being on APT, especially with regard to bleeding and the influence of different PDT techniques. Material and Methods: Between July 2016 and June 2021, 273 intensive care unit (ICU) patients underwent in-house PDT with two different techniques (direct or indirect) and were retrospectively enrolled. Results: A total of 273 patients (mean age: 68 years, 37% female) were included in the study. A total of 51% of patients were on APT on the day of PDT procedure (SAPT: 34%, DAPT: 17%). Direct and indirect PDTs were performed in 33% and 67% of patients. Periprocedural airway or skin bleedings and postprocedural bleedings occurred in 53%, 11%, and 1%. A need for bronchoscopic re-intervention was observed in 2% of APT patients. No death was procedure related. Periprocedural airway bleedings occurred more frequent in “APT patients” (60% vs. 46%, p = 0.03). Periprocedural airway and skin bleedings were more frequent in indirect PDTs (52% and 14%) than direct PDTs (32% and 0%, p = 0.04 and p = 0.02) in “no APT patients”. In “APT patients” this difference was only seen in periprocedural airway bleeding (69% vs. 45%, p = 0.01). Moreover, periprocedural airway bleedings were more frequent in “APT patients” when performing an indirect PDT rather than a direct PDT (69% vs. 52%, p = 0.02). Conclusions: PDTs appear to be safe in patients receiving APT. Indirect PDTs appear to generally increase the risk of clinically irrelevant, minor periprocedural airway and possibly skin bleedings, especially in APT patients. Full article

Background/Objectives: Large clinical trials have established the optimal antiplatelet strategy in the wide spectrum of coronary artery disease. However, data are scarce regarding MINOCA and the aim of our study is to present data from the current clinical practice. Methods: A total of 151 patients were included in this study after exclusion of 27 patients with myocarditis and other diagnoses. A cardiac magnetic resonance (CMR) performed at 123/151 patients demonstrated an ischemic pattern of late gadolinium enhancement (LGE) confirming the diagnosis of true acute myocardial infarction (AMI) in 42 cases (28%). Based on multimodality imaging and clinical judgement, Takotsubo syndrome (TTS) was diagnosed in 55 patients (36%), whereas CMR failed to reveal abnormal findings in 54 cases (36%), categorized as MINOCA of unknown origin. Results: Regarding antithrombotic prescriptions at discharge, 38% of patients received dual antiplatelet (DAPT) or dual antithrombotic therapy (DAT, 1 antiplatelet plus 1 anticoagulant), 49.7% received single antiplatelet (SAPT) or anticoagulant, and 12% received no antithrombotic treatment. Univariate analysis showed that the likelihood of prescribing DAPT or DAT was associated with left ventricular ejection fraction (LVEF) (r = 0.202, p = 0.013), atherosclerotic lesions on coronary angiography (r = 0.303, p < 0.001), prior use of anticoagulants (r = −0.258, p = 0.001), and marginally with the INTERTAK score (r = −0.198, p = 0.044). A multivariable model, adjusted for age, LVEF, ECG abnormalities, and history of anticoagulant use, confirmed the independent association between angiographic evidence of atherosclerosis and the decision for DAPT/DAT (OR: 0.334, 95% CI: 0.307–0.813, p < 0.001). However, the initial treatment decision did not seem to impact 2-year prognosis in our population. Conclusions: Our study results reveal that decision making in the antithrombotic strategy for MINOCA patients poses a challenge in clinical practice. More robust data are required for definite conclusions on the prognostic implications. Full article

Background: Atrial fibrillation (AF) is prevalent in patients undergoing transcatheter aortic valve replacement (TAVR). However, the optimal antithrombotic strategy tailored to individual patient profiles remains unclear. This study aims to evaluate the outcomes of personalized antithrombotic regimens in patients with AF after TAVR. Methods: We enrolled 121 AF patients who underwent TAVR from 2009 to 2023. Patients were grouped into seven groups based on individualized post-procedural antithrombotic regimens. The regimens included the following: single antiplatelet therapy (SAPT) + direct oral anticoagulant (DOAC) (n = 44, 36.3%); DOACs only (n = 25, 20.6%), SAPT + warfarin (n = 17, 14%); dual antiplatelet therapy (DAPT) (n = 13, 10.7%); warfarin only (n = 8, 6.6%); DAPT + warfarin (n = 7, 5.8%); and DAPT + DOACs (n = 7, 5.8%). The study outcomes included incidences of strokes or transient ischemic attacks (TIAs), major bleeding, and survival. Results: The median follow-up was 27 months. The incidence of stroke, TIA, or major bleeding was similar among the seven treatment groups. However, a trend toward a higher rate of stroke was observed in the triple regimen containing warfarin (28.6%); also, the highest rate of major bleeding was observed in the warfarin-only group (25%). Survival for patients discharged and placed under various antithrombotic regimens did not differ significantly despite some numerical variations being present across the groups, with the lowest mortality reported with SAPT + warfarin (7%) and the highest with DAPT + warfarin (57%). Conclusions: This study highlights the outcomes related to stroke, major bleeding, and mortality across personalized antithrombotic regimens in patients with AF after TAVR. While no statistically significant differences were observed, findings emphasize the need for further large-scale studies to define optimal personalized antithrombotic strategies based on individual patient characteristics. Full article

To explore the impact of different substituents (R) in 4-R-1,5-diaminotetrazolium cations on the performance of their pentazolate salts, five types of pentazolate salts with different groups were designed: -H, -OH, -NH₂, -NH-NH₂, and -N₃. Quantum chemical methods were employed to deeply study the interionic interactions and detonation properties of these 4-R-1,5-diaminotetrazolium pentazolate salts. Among these five ionic compounds, the 1,5-diamino-4-hydroxytetrazolium pentazolate ([DAT-OH⁺] [N₅⁻]) system exhibited the lowest interaction energy and highest stability, while the 1,5-diamino-1H-1,2,3,4-tetrazolium pentazolate ([DAT-H⁺] [N₅⁻]) system was the least stable. Symmetry-adapted perturbation theory (SAPT) analysis indicated that electrostatic and dispersion effects predominantly contributed to these interactions. An independent gradient model based on Hirshfeld partition (IGMH) analysis further highlighted the interionic interaction regions, revealing extensive van der Waals interactions and the formation of N-H…N type hydrogen bonds. The hydrogen bond formed by the cyclo-N₅⁻ and hydroxyl groups was relatively strong, while other hydrogen bonds were weaker. Benefiting from a higher enthalpy of formation, the 1,5-diamino-4-azidotetrazolium pentazolate ([DAT-N₃⁺] [N₅⁻]) compound exhibited the highest detonation performance (D: 9295.77 m·s⁻¹; P: 32.13 GPa), while [DAT-OH⁺] [N₅⁻] also demonstrated good performance and stability (D: 8924.96 m·s⁻¹; P: 28.85 GPa). Full article

The present work deals with the computational study of HC₃N$··$HCN$··$H₂C₂-, (HC₃N)₂$··$H₂C₂-, and HC₃N$··$(H₂C₂)₂-mixed trimers. The different equilibrium structures of the different low-lying minima on the corresponding potential energy surface (PES) were accurately determined, and the relative stabilities were computed by extrapolation procedures to the complete basis set limit. For each mixed trimer, the non-covalent interactions ruling the structure of the most stable isomer were analyzed using the QTAIM (Quantum Theory of Atoms in Molecules) approach. Additional insights into these interactions were provided by the Natural Bond Orbital (NBO) and Symmetry-Adapted Perturbation Theory (SAPT) methods. These results can be used to assist further theoretical investigations and experimental studies on the formation of larger molecules potentially relevant in astrochemistry. Full article

The objective of this study was to investigate the effects on laying performance, egg quality traits, color, and composition of supplementing a white corn-based diet with Desmodium tortuosum leaf flour. Three hundred 32-week-old hens were distributed to 30 pens of 10 hens each and allocated to six dietary treatments (five replicates per treatment) for 13 weeks. Two control groups of 50 hens received one of either diet Y, based on yellow corn, or diet W, based on white corn. The other groups received a diet based on white corn supplemented with Desmodium tortuosum leaf flour at 2.5%, 5%, 7.5%, or 10% (diet D). Diet D improved laying performance and yolk color at a reduced feed cost per egg but had no effect on cholesterol content. In conclusion, the inclusion of Desmodium tortuosum leaf flour, in a white corn-based diet, is effective in lowering feed cost, increasing egg production, and improving yolk color. Full article

The development of drug resistance in cancer cells poses a significant challenge for treatment, with nearly 90% of cancer-related deaths attributed to it. Over 50% of ovarian cancer patients and 30–40% of breast cancer patients exhibit resistance to therapies such as Taxol. Previous literature has shown that cytotoxic cancer therapies and ionizing radiation damage tumors, prompting cancer cells to exploit the autotaxin (ATX)–lysophosphatidic acid (LPA)–lysophosphatidic acid receptor (LPAR) signaling axis to enhance survival pathways, thus reducing treatment efficacy. Therefore, targeting this signaling axis has become a crucial strategy to overcome some forms of cancer resistance. Addressing this challenge, we identified and assessed ATX-1d, a novel compound targeting ATX, through computational methods and in vitro assays. ATX-1d exhibited an IC₅₀ of 1.8 ± 0.3 μM for ATX inhibition and demonstrated a significant binding affinity for ATX, as confirmed by MM-GBSA, QM/MM-GBSA, and SAPT in silico methods. ATX-1d significantly amplified the potency of paclitaxel, increasing its effectiveness tenfold in 4T1 murine breast carcinoma cells and fourfold in A375 human melanoma cells without inducing cytotoxic effects as a single agent. Full article

The benzene dimer (BD) is an archetypal model of π∙∙∙π and C–H∙∙∙π noncovalent interactions as they occur in its cofacial and perpendicular arrangements, respectively. The enthalpic stabilization of the related BD structures has been debated for a long time and is revisited here. The revisit is based on results of computations that apply the coupled-cluster theory with singles, doubles and perturbative triples [CCSD(T)] together with large basis sets and extrapolate results to the complete basis set (CBS) limit in order to accurately characterize the three most important stationary points of the intermolecular interaction energy (ΔE) surface of the BD, which correspond to the tilted T-shaped (TT), fully symmetric T-shaped (FT) and slipped-parallel (SP) structures. In the optimal geometries obtained by searching extensive sets of the CCSD(T)/CBS ΔE data of the TT, FT and SP arrangements, the resulting ΔE values were −11.84, −11.34 and −11.21 kJ/mol, respectively. The intrinsic strength of the intermolecular bonding in these configurations was evaluated by analyzing the distance dependence of the CCSD(T)/CBS ΔE data over wide ranges of intermonomer separations. In this way, regions of the relative distances that favor BD structures with either π∙∙∙π or C–H∙∙∙π interactions were found and discussed in a broader context. Full article

The rotational spectra of the 1:1 complex formed by acrolein and methanol and its deuterated isotopologues have been analyzed. Two stable conformations in which two hydrogen bonds between the two moieties are formed were detected. The rotational lines show a hyperfine structure due to the methyl group internal rotation in the complex and the V₃ barriers hindering the motion were determined as 2.629(5) kJ mol⁻¹ and 2.722(5) kJ mol⁻¹ for the two conformations, respectively. Quantum mechanical calculations at the MP2/aug-cc-pVTZ level and comprehensive analysis of the intermolecular interactions, utilizing NCI and SAPT approaches, highlight the driving forces of the interactions and allow the determination of the binding energies of complex formation. Full article

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structure and function, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides’ structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragments and water were analyzed. Different quantum mechanical methods were compared for their accuracy in capturing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These calculations provide a benchmark for different QM methods, in addition to providing a valuable understanding of the roles of various intermolecular forces in hydrogen bonding and aromatic stacking. With SAPT, a higher theory level and/or larger basis set did not necessarily give more accuracy. It is hard to know which combination would be best for a given system. In contrast, ALMO EDA2 did not show dependence on theory level or basis set; additionally, it is faster. Full article

Solid-state drug delivery systems for the drug substances transport are of great importance nowadays. In the present work, the non-covalent interactions between taxifolin (Tax) and graphene as well as nitrogenated (N-doped) graphenes were systematically studied by using a wide set of theoretical techniques. Symmetry-adapted perturbation theory (SAPT0) calculations confirmed more favorable adsorption of Tax on N-doped graphenes compared to pristine graphene. It was established that dispersion interactions play the main role in the attractive interactions (>60%), whereas electrostatic and induction forces contribute only moderately to the attraction (~25% and 7–8%, respectively). Independent gradient model (IGM) analysis visually demonstrated the existence of dispersion interactions and hydrogen bonding in the studied Tax complexes. Ab initio molecular dynamics calculations indicated stability of these complexes at different temperatures. Our results show that N-doped graphenes with the enhanced interaction energy (E_int) toward Tax are promising candidates for the technical realization of the targeted drug delivery systems. Full article

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment. Full article

This study reveals a new non-covalent interaction called a π-hole halogen bond, which is directional and potentially non-linear compared to its sister analog (σ-hole halogen bond). A π-hole is shown here to be observed on the surface of halogen in halogenated molecules, which can be tempered to display the aptness to form a π-hole halogen bond with a series of electron density-rich sites (Lewis bases) hosted individually by 32 other partner molecules. The [MP2/aug-cc-pVTZ] level characteristics of the π-hole halogen bonds in 33 binary complexes obtained from the charge density approaches (quantum theory of intramolecular atoms, molecular electrostatic surface potential, independent gradient model (IGM-δg^inter)), intermolecular geometries and energies, and second-order hyperconjugative charge transfer analyses are discussed, which are similar to other non-covalent interactions. That a π-hole can be observed on halogen in halogenated molecules is substantiated by experimentally reported crystals documented in the Cambridge Crystal Structure Database. The importance of the π-hole halogen bond in the design and growth of chemical systems in synthetic chemistry, crystallography, and crystal engineering is yet to be fully explicated. Full article