Oral anticoagulation for atrial fibrillation in the era of non-vitamin K antagonist anticoagulants. Focus on very elderly patients

Introduction. Atrial fibrillation is the most common cardiac arrhythmia, characterized by irregular heart rhythm and associated with left atrial and left appendage thrombi formation that may cause ischemic stroke. Oral anticoagulant therapy has been shown to reduce the incidence of ischemic stroke in these patients by about two thirds, at the expense of an increase in bleeding. In the elderly, atrial fibrillation is particularly frequent, but anticoagulant therapy often encounter several issues: in fact, although ischemic risk increases with age, haemorrhagic risk is also high and often doctors prefers not to prescribe or discontinue oral anticoagulant therapy in fear of complications. The elderly patient, moreover, is often affected by multiple diseases, takes several drugs with potential risk of interactions and may have lower adherence to therapy. Aim. To evaluate the impact of anticoagulation in the elderly patient, focusing on the subgroup of very elderly patients (i.e. 80 years of age) who are often not included in major clinical trials. VENPAF. We initially conducted a retrospective "inception cohort" study involving all patients 80 years of age referred to the local Thrombosis Centre to start anticoagulant therapy with warfarin for atrial fibrillation (VENPAF study). From data analysis, we found that major haemorrhages rate is very high and tends to increase considerably over 85 years of age. Nevertheless, net clinical benefit appears to be maintained, as the calculated incidence of thromboembolism in the absence of anticoagulant therapy was higher in both age classes compared to the observed incidence of major haemorrhages. About 20% of these patients had discontinued warfarin and this was often decided by the general practitioner or the specialist; main reasons for discontinuation were low life expectancy, fragility and excessive haemorrhagic risk. We found that therapy discontinuation was not associated with an improvement in prognosis, but indeed these patients faced high rates of mortality, ischemic and haemorrhagic events, regardless of persistence or discontinuation of anticoagulant therapy. Analysing only patients who experienced a major bleeding event during anticoagulant therapy, we could highlight how the cumulative incidence of ischemic and haemorrhagic events was significantly higher in patients who suspended therapy than those who resumed it after the index event.control study. A case-control study was set to analyse which factors may possibly be associated with the development of intracranial haemorrhage with warfarin (the most serious complication of oral anticoagulant therapy). All patients followed by our Thrombosis Centre who developed intracranial bleeding in anticoagulant therapy were included; control group was created from anticoagulated patients paired for age, sex, and exposure to therapy in a 1:4 ratio. No variable was associated with the development of bleeding. We also could evaluate ischemic risk for each patient using HAS-BLED, ATRIA and ORBIT haemorrhage scores; these scores showed a predisposing capacity for particularly poor intracranial haemorrhage (c-statistic around 0.55 for all three scores). Veneto Region Registry. After the analysis of cerebral bleedings during warfarin therapy, we focused on the use of non-vitamin K oral anticoagulants (NOAC), which demonstrated to halve cerebral bleeding as compared with warfarin in clinical trials. Using Veneto Region registries of pharmacological prescriptions, exemptions, and department discharge diagnoses, we were able to select patients who started oral anticoagulant therapy because of non-valvular atrial fibrillation and compared patients who started warfarin therapy versus those who started a NOAC. Results were broadly consistent with the literature, with similar efficacy and safety but a sharp reduction in intracranial bleedings and a mild reduction in mortality with NOAC, despite the good quality of warfarin anticoagulation achieved thanks to the thrombosis centers of our regions. Moreover, we found that patients treated with NOAC in Veneto region are on average older and at higher ischemic risk than patients treated with warfarin. Finally, we analysed the subset of patients ≥80 years old and found a marked increase in gastrointestinal bleeding, especially from the lower tract, in patients treated with NOAC. However, ischemic stroke and total major bleedings rates were similar among the two groups and NOAC patients showed a lower risk of intracranial haemorrhage. Conclusions. The present work analysed the effects of anticoagulant therapy in elderly patients with 80 years or more. Based on the different studies we conducted, it was possible to conclude that, despite the high risk of haemorrhage, clinical benefit for the prevention of stroke is in favour for the use of these drugs in this subset of patients. In fact, patients who suspended anticoagulant treatment had a worse prognosis than patients who persisted. Intracranial hemorrhage is the most fearful side effect of anticoagulant treatment, being related to very high rates of mortality and disability; from our findings, these events are more frequent in the elderly and are not predictable by common cardiovascular risk factors or good anticoagulation quality. Data on NOAC users, on the other hand, seem to confirm that the risk of intracranial bleeding is inferior to warfarin even in the very elderly, despite a significant increase in the risk of gastrointestinal haemorrhage. Overall, therefore, our data confirms NOAC as the preferred anticoagulant therapy in very elderly patients with non-valvular atrial fibrillation

Strong electronic correlations in Lix_xZnPc organic metals

Nuclear magnetic resonance, electron paramagnetic resonance and magnetization measurements show that bulk Li$_x$ZnPc are strongly correlated one-dimensional metals. The temperature dependence of the nuclear spin-lattice relaxation rate $1/T_1$ and of the static uniform susceptibility $\chi_S$ on approaching room temperature are characteristic of a Fermi liquid. Moreover, while for $x\simeq 2$ the electrons are delocalized down to low temperature, for $x\to 4$ a tendency towards localization is noticed upon cooling, yielding an increase both in $1/T_1$ and $\chi_s$. The $x$-dependence of the effective density of states at the Fermi level $D(E_F)$ displays a sharp enhancement for $x\simeq 2$, at the half filling of the ZnPc lowest unoccupied molecular orbitals. This suggests that Li$_x$ZnPc is on the edge of a metal-insulator transition where enhanced superconducting fluctuations could develop.Comment: 5 pages, 4 figure

Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)- and 2-oxoglutarate-dependent decarboxylase ALKBH4

The Fe(II)/2OG (2-oxoglutarate)-dependent dioxygenase superfamily comprises proteins that couple substrate oxidation to decarboxylation of 2OG to succinate. A member of this class of mononuclear non-haem Fe proteins is the Escherichia coli DNA/RNA repair enzyme AlkB. In the present work, we describe the magnetic and optical properties of the yet uncharacterized human ALKBH4 (AlkB homologue). Through EPR and UV–visible spectroscopy studies, we address the Fe-binding environment of the proposed catalytic centre of wild-type ALKBH4 and an Fe(II)-binding mutant. We could observe a novel unusual Fe(III) high-spin EPR-active species in the presence of sulfide with a gmax of 8.2. The Fe(II) site was probed with NO. An intact histidine-carboxylate site is necessary for productive Fe binding. We also report the presence of a unique cysteine-rich motif conserved in the N-terminus of ALKBH4 orthologues, and investigate its possible Fe-binding ability. Furthermore, we show that recombinant ALKBH4 mediates decarboxylation of 2OG in absence of primary substrate. This activity is dependent on Fe as well as on residues predicted to be involved in Fe(II) co-ordination. The present results demonstrate that ALKBH4 represents an active Fe(II)/2OG-dependent decarboxylase and suggest that the cysteine cluster is involved in processes other than Fe co-ordination

Excitation Wavelength- and Medium-Dependent Photoluminescence of Reduced Nanostructured TiO2 Films

The performance of TiO2 nanomaterials in solar energy conversion applications can be tuned by means of thermal treatments in reducing atmospheres, which introduce defects (such as oxygen vacancies), allowing, for instance, a better charge transport or a higher photocatalytic activity. The characterization of these defects and the understanding of their role are pivotal to carefully engineer the properties of TiO2, and, among various methods, they have been addressed by photoluminescence (PL) spectroscopy. A definitive framework to describe the PL properties of TiO2, however, is still lacking. In this work, we report on the PL of nanostructured anatase TiO2 thin films, annealed in different atmospheres (oxidizing and reducing), and consider the effects of different excitation energies and different surrounding media on their PL spectra. A broad PL signal centered around 1.8–2.0 eV is found for all the films with UV excitation in air as well as in vacuum, while the same measurements in ethanol lead to a blueshift and to intensity changes in the spectra. On the other hand, measurements with different sub-bandgap excitations show PL peaking at 1.8 eV, with an intensity trend only dependent on the thermal treatment and not on the surrounding medium. The results of PL spectroscopy, together with electron paramagnetic resonance spectroscopy, suggest the critical role of oxygen vacancies and Ti3+ ions as radiative recombination centers. The complex relationship between thermal treatments and PL data in the explored conditions is discussed, suggesting the importance of such investigations for a deeper understanding on the relationship between defects in TiO2 and photoactivity

A novel mixed valence form of Rhus vernicifera laccase and its reaction with dioxygen to give a peroxide intermediate bound to the trinuclear center

金沢大学理工研究域物質化学系Rhus vernicifera laccase, in a novel mixed valence state [T1oxT23red: type 1 Cu as Cu(II), and type 2 and 3 Cus as Cu(I)], was formed by reacting Cu(I) on the type 2 Cudepleted laccase [T1oxT3red: type 1 Cu as Cu(II) and type 3 Cus as Cu(I)] under argon. Contrary to T1oxT3red, T1oxT23red was highly reactive with dioxygen, and gave the three transient bands at 340, 475, and 680 nm due to the two-electron reduced form of dioxygen [charge transfer bands from peroxide to Cu(II)]. The first order decays were highly dependent on pH, which led to the successful detection of the intermediate for ca. 2 h at pH 7.5. Another mixed valence derivative, T12oxT3red [type 1 and type 2 Cus as Cu(II), and type 3 Cus as Cu(I)] prepared through the action of Cu(II) on T1oxT3red was not reactive with dioxygen, but showed high enzyme activity as to the oxidation of N,N-dimethyl-p-phenylenediamine. The whole reaction mechanism of the reduction of dioxygen by laccase was proposed based on the present results together with data for the former detection and characterization of the three-electron reduced form of dioxygen

Graphene Acid for Lithium‐Ion Batteries—Carboxylation Boosts Storage Capacity in Graphene

Environmentally sustainable, low-cost, flexible, and lightweight energy storage technologies require advancement in materials design in order to obtain more efficient organic metal-ion batteries. Synthetically tailored organic molecules, which react reversibly with lithium, may address the need for cost-effective and eco-friendly anodes used for organic/lithium battery technologies. Among them, carboxylic group-bearing molecules act as high-energy content anodes. Although organic molecules offer rich chemistry, allowing a high content of carboxyl groups to be installed on aromatic rings, they suffer from low conductivity and leakage to the electrolytes, which restricts their actual capacity, the charging/discharging rate, and eventually their application potential. Here, a densely carboxylated but conducting graphene derivative (graphene acid (GA)) is designed to circumvent these critical limitations, enabling effective operation without compromising the mechanical or chemical stability of the electrode. Experiments including operando Raman measurements and theoretical calculations reveal the excellent charge transport, redox activity, and lithium intercalation properties of the GA anode at the single-layer level, outperforming all reported organic anodes, including commercial monolayer graphene and graphene nanoplatelets. The practical capacity and rate capability of 800 mAh g−1 at 0.05 A g−1 and 174 mAh g−1 at 2.0 A g−1 demonstrate the true potential of GA anodes in advanced lithium-ion batteries

Metastable Ni(I)-TiO _2-x Photocatalysts: Self-Amplifying H₂ Evolution from Plain Water without Noble Metal Co-Catalyst and Sacrificial Agent

Decoration of semiconductor photocatalysts with cocatalysts is generally done by a step-by-step assembly process. Here, we describe the self-assembling and self-activating nature of a photocatalytic system that forms under illumination of reduced anatase TiO2 nanoparticles in an aqueous Ni2+ solution. UV illumination creates in situ a Ni+/TiO2/Ti3+ photocatalyst that self-activates and, over time, produces H-2 at a higher rate. In situ X-ray absorption spectroscopy and electron paramagnetic resonance spectroscopy show that key to self-assembly and self-activation is the light-induced formation of defects in the semiconductor, which enables the formation of monovalent nickel (Ni+) surface states. Metallic nickel states, i.e., Ni-0, do not form under the dark (resting state) or under illumination (active state). Once the catalyst is assembled, the Ni+ surface states act as electron relay for electron transfer to form H-2 from water, in the absence of sacrificial species or noble metal cocatalysts.Web of Science14548261322612

Unveiling the potential of covalent organic frameworks for energy storage: Developments, challenges, and future prospects

Covalent organic frameworks (COFs) are porous structures emerging as promising electrode materials due to their high structural diversity, controlled and wide pore network, and amenability to chemical modifications. COFs are solely composed of periodically arranged organic molecules, resulting in lightweight materials. Their inherent properties, such as extended surface area and diverse framework topologies, along with their high proclivity to chemical modification, have positioned COFs as sophisticated materials in the realm of electrochemical energy storage (EES). The modular structure of COFs facilitates the integration of key functions such as redox‐active moieties, fast charge diffusion channels, composite formation with conductive counterparts, and highly porous network for accommodating charged energy carriers, which can significantly enhance their electrochemical performance. However, ascribing intricate porosity and redox‐active functionalities to a single COF structure, while maintaining long‐term electrochemical stability, is challenging. Efforts to overcome these hurdles embrace strategies such as the implementation of reversible linkages for structural flexibility, stimuli‐responsive functionalities, and incorporating chemical groups to promote the formation of COF heterostructures. This review focuses on the recent progress of COFs in EES devices, such as batteries and supercapacitors, through a meticulous exploration of the latest strategies aimed at optimizing COFs as advanced electrodes in future EES technologies