Molecular ruthenium‐based water oxidation catalyst precursors of general formula Ru(tda)(Li)2 (tda2− is 2,2′:6′,2′′‐terpyridine‐6,6′′‐dicarboxylato; ...L1=4‐(pyren‐1‐yl)‐N‐(pyridin‐4‐ylmethyl)butanamide, 1 b; L2=4‐(pyren‐1‐yl)pyridine), 1 c), have been prepared and thoroughly characterized. Both complexes contain a pyrene group allowing ready and efficiently anchoring via π interactions on multi‐walled carbon nanotubes (MWCNT). These hybrid solid state materials are exceptionally stable molecular water‐oxidation anodes capable of carrying out more than a million turnover numbers (TNs) at pH 7 with an Eapp=1.45 V vs. NHE without any sign of degradation. XAS spectroscopy analysis before, during, and after catalysis together with electrochemical techniques allow their unprecedented oxidative ruggedness to be monitored and verified.
A million TONs: Oxidatively stable molecular water oxidation anodes reaching more than a million turnover numbers with no molecular degradation are achieved by using a ruthenium‐based molecular catalyst anchored on a multi‐walled carbon nanotube.
Analogously to enzymatic catalysis, where the active metal sites and their environment are controlled by protein residues, the catalytic properties of metal nanoparticles (NPs) can be tuned by ...carefully selecting their surface‐coordinated species. In artificial photosynthesis, surface‐functionalization emerged in the last decade, grounded on the development of reliable methods for tailored synthesis, advanced characterization and theoretical modeling of metal NPs, altogether with the aim of transferring to the nanoscale the mechanistic knowledge acquired from molecular complexes. Metal NPs surface‐functionalization modulates the energetics of key catalytic intermediates, introduces second coordination sphere effects, influences the catalyst‐electrolyte interface, and determines the metal NPs surface coverage and, accordingly, the number of accessible active sites. In photoactivated systems, metal NPs surface‐functionalization may play a key role in modulating the charge transfers and recombination processes between the light absorber and the active sites and in the light absorber itself. Thus, after a presentation of the most relevant synthetic methods to produce well‐defined surface‐functionalized metal NPs, a critical analysis of why the above effects are the cornerstone in enhancing their catalytic performance in the key processes of artificial photosynthesis, namely the oxygen evolution reaction, the hydrogen evolution reaction, and the CO2 reduction reaction, is given.
Nanoparticle surface‐functionalization is an emerging strategy to enhance the catalysis of artificial photosynthesis. This review presents a critical analysis of the most remarkable examples reported to date with the aim to shed light on the role of surface ligands in each of the followingreactions: oxygen evolution reaction, hydrogen evolution reaction, and CO2 reduction reaction.
A cobalt complex bearing a κ‐N3P2 ligand is presented (1+ or CoI(L), where L is (1E,1′E)‐1,1′‐(pyridine‐2,6‐diyl)bis(N‐(3‐(diphenylphosphanyl)propyl)ethan‐1‐imine). Complex 1+ is stable under air at ...oxidation state CoI thanks to the π‐acceptor character of the phosphine groups. Electrochemical behavior of 1+ reveals a two‐electron CoI/CoIII oxidation process and an additional one‐electron reduction, which leads to an enhancement in the current due to hydrogen evolution reaction (HER) at Eonset=−1.6 V vs Fc/Fc+. In the presence of 1 equiv of bis(trifluoromethane)sulfonimide, 1+ forms the cobalt hydride derivative CoIII(L)‐H (22+), which has been fully characterized. Further addition of 1 equiv of CoCp*2 (Cp* is pentamethylcyclopentadienyl) affords the reduced CoII(L)‐H (2+) species, which rapidly forms hydrogen and regenerates the initial CoI(L) (1+). The spectroscopic characterization of catalytic intermediates together with DFT calculations support an unusual bimolecular homolytic mechanism in the catalytic HER with 1+.
A CoI complex bearing a redox‐active κ‐N3P2 pentadentate ligand and its activity towards hydrogen evolution reaction is reported in this work. A combination of spectroscopic, electrochemical and computational techniques is employed to characterize the intermediate species, demonstrating an unusual homolytic coupling reaction pathway between two catalyst units.
Different diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)-familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever ...syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)-and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.
Step 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients' diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of the best candidate classification criteria; step 4: nominal group technique consensus conference with 33 panellists for the discussion and selection of the final classification criteria; step 5: cross-sectional validation of the novel criteria.
The panellists achieved consensus to classify 281 of 360 (78%) patients (32 CAPS, 36 FMF, 56 MKD, 37 PFAPA, 39 TRAPS, 81 undefined recurrent fever). Consensus was reached for two sets of criteria for each HRF, one including genetic and clinical variables, the other with clinical variables only, plus new criteria for PFAPA. The four HRF criteria demonstrated sensitivity of 0.94-1 and specificity of 0.95-1; for PFAPA, criteria sensitivity and specificity were 0.97 and 0.93, respectively. Validation of these criteria in an independent data set of 1018 patients shows a high accuracy (from 0.81 to 0.98).
Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.
: Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. ...In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with ≥80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD.
Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) ...MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2-specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-Cplus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.
Four different cathodes for the hydrogen evolution reaction (HER) have been developed by the decoration of commercial carbon microfibers with Ru nanoparticles (Ru NPs). Two types of carbon fibers ...have been used: pristine, as‐received, carbon fibers (pCF) and carbon fibers modified by an oxidative treatment that led to the functionalization of their surface with carboxylic groups (fCF). The decoration of these CFs with Ru NPs has been performed by two different methodologies based on the organometallic approach: direct synthesis of Ru NPs on top of the CFs (in‐situ Ru NPs) or impregnation of the CFs with a colloidal solution of preformed Ru NPs stabilized with 4‐phenylpyridine (RuPP NPs; ex‐situ Ru NPs). The electrocatalytic performance of these four cathodes (ex‐situ RuPP@pCF and RuPP@fCF; in‐situ Ru@pCF and Ru@fCF) for the HER has been studied in acidic conditions. The results obtained show that both the nature of the NPs and of the carbon fibers play a key role on the stability and activity of the hybrid electrodes: ex‐situ prepared Ru NPs afford better activities at lower overpotentials and better stabilities than those formed in‐situ. Among the two ex‐situ systems, an enhancement of the stability with pCF is observed, that may arise from more effective π‐interactions between 4‐phenylpyridine ligand and the surface of these carbon fibers. This interaction is somehow disfavored with fCF due to the presence of the surface carboxylic groups.
Four heterogeneous hybrid cathodes for the catalytic hydrogen evolution reaction (HER) have been prepared combining two types of carbon fibers and two different synthetic methodologies in order to decorate their surface with Ru nanoparticles. The activity and stability of all the hybrid systems have been evaluated.
To identify the clinical characteristics, reasons for use and response to treatment with anakinra in a series of patients with Kawasaki Disease (KD).
A retrospective chart review of patients treated ...with anakinra for KD diagnosed according to the AHA criteria. We compared clinical, biological and echocardiographic characteristics of KD before and after anakinra use. We analysed reasons for use of anakinra, and compared treatment regimens used in 7 European KD referral centres.
Eight boys and 3 girls with treatment-refractory KD, aged 4 months to 9 years old, received at least 2 different KD treatments prior to anakinra, which was given on mean at 25 days after disease onset (8 to 87 days). The main reasons for use of anakinra were clinical and biological inflammation, progression of coronary dilatations, and severe myocarditis with cardiac failure. Doses of anakinra ranged from 2 to 8 mg/kg and duration varied from 6 to 81 days. Efficacy of anakinra was judged in terms of fever resolution (100%), decrease of CRP (100%), and in terms of its effect on coronary artery dilatation Z scores, which decreased in 10/11 patients and increased in one who died suddenly of pericardial hemorrhage.
Anakinra used late in the disease course led to a rapid and sustained improvement in clinical and biological inflammation. Our retrospective analysis did show neither a striking nor a rapid decrease of coronary dilatations and we cannot determine if anakinra itself had an effect on coronary artery dimensions.
Objective
Mevalonate kinase deficiency (MKD) is a rare metabolic disease characterized by recurrent inflammatory episodes. This study was undertaken to describe the genotype, phenotype, and response ...to treatment in an international cohort of MKD patients.
Methods
All MKD cases were extracted from the Eurofever registry (Executive Agency for Health and Consumers project no. 2007332), an international, multicenter registry that retrospectively collects data on children and adults with autoinflammatory diseases.
Results
The study included 114 MKD patients. The median age at onset was 0.5 years. Patients had on average 12 episodes per year. Most patients had gastrointestinal symptoms (n = 112), mucocutaneous involvement (n = 99), lymphadenopathy (n = 102), or musculoskeletal symptoms (n = 89). Neurologic symptoms included headache (n = 43), cerebellar syndrome (n = 2), and mental retardation (n = 4). AA amyloidosis was noted in 5 patients, almost twice as many as expected from findings in previous cohorts. Macrophage activation syndrome occurred in 1 patient. Patients were generally well between attacks, but 10–20% of the patients had constitutional symptoms, such as fatigue, between fever episodes. Patients with p.V377I/p.I268T compound heterozygosity had AA amyloidosis significantly more often. Patients without a p.V377I mutation more often had severe musculoskeletal involvement. Treatment with nonsteroidal antiinflammatory drugs relieved symptoms. Steroids given during attacks, anakinra, and etanercept appeared to improve symptoms and could induce complete remission in patients with MKD.
Conclusion
We describe the clinical and genetic characteristics of 114 MKD patients, which is the largest cohort studied so far. The clinical manifestations confirm earlier reports. However, the prevalence of AA amyloidosis is far higher than expected.
Abstract
Objectives
Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions. ...The aim of this study was to evaluate the demographic data and clinical, instrumental and therapeutic features at baseline in a large series of CNO/CRMO patients enrolled in the Eurofever registry.
Methods
A web-based registry collected retrospective data on patients affected by CRMO/CNO. Both paediatric and adult centres were involved.
Results
Complete baseline information on 486 patients was available (176 male, 310 female). The mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in 31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1 year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing a mean number of 4.1 lesions. More frequent manifestations not directly related to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5% palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial rash) and gastrointestinal symptoms (8%). A total of 361 patients have been treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response.
Conclusion
This is the largest reported case series of CNO patients, showing that the range of associated clinical manifestations is rather heterogeneous. The study confirms that the disease usually presents with an early teenage onset, but it may also occur in adults, even in the absence of mucocutaneous manifestations.
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